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1
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Chen YJ, Chang TY, Chen CH. Unraveling the association between chronic inflammatory demyelinating polyradiculoneuropathy and peritoneal Dialysis. BMC Nephrol 2024; 25:383. [PMID: 39468467 PMCID: PMC11514778 DOI: 10.1186/s12882-024-03830-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 10/21/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease seen in the general population and has been reported as showing an increased incidence in the peritoneal dialysis (PD) population, as documented in case reports. METHODS We conducted a case-control study using data from the Taichung Veterans General Hospital electric medical record database from the years 2010 to 2023. We defined cases as CIDP with End-stage kidney disease (ESKD) and controls as without CIDP. A logistic regression analysis was used to investigate the association between CIDP and dialysis modality, age, gender, dialysis duration, plasma potassium > 5.5 mEq/L and < 2.5 mEq/L, and intact parathyroid hormone (i-PTH) > 613 pg/mL. RESULTS Our findings suggest that PD may be a risk factor in the ESKD population (Odds ratio: 5.125, C.I.: 1.078 ~ 24.372, p = 0.040) according to logistic regression analysis. Dialysis duration, gender, diabetes mellitus, HbA1c > 7%, hypokalemia, hyperkalemia, and hyperparathyroidism did not show an association with CIDP. CONCLUSION There seems to be an association between PD and CIDP in this case-control study. Possible mechanisms may involve systemic inflammation induced by peritoneal dialysate exchange or the content of the dialysate. Further studies are still needed.
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Affiliation(s)
- Yu-Jen Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ting-Ya Chang
- Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
- Department of Life Science, Tunghai University, Taichung, Taiwan.
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Abstract
The peritoneal cavity is a fluid-packed area that houses most of the abdominal organs, including the omentum, a visceral adipose tissue with milky patches or groups of leukocytes organized in the same way to those observed in typical lymphoid tissues. A distinct population of leukocytes patrols the peritoneal cavity and travels in and out of the milky spots, facing antigens or pathogens in the peritoneal fluid and responding appropriately. T cells may play a crucial function in regulating adaptive immune responses to antigens in the peritoneal cavity to ensure tissue homeostasis and healing. When peritoneal homeostasis is interrupted by inflammation, infection, obesity, or tumor metastasis, the omentum's dedicated fibroblastic stromal cells and mesothelial cells control peritoneal leukocyte recruitment and activation in unique ways. T cells, which employ their T cell receptor to target specific antigens, are an important component of the acquired immune response since they are present in the peritoneal cavity. The peritoneum provides a different environment for T cells to respond to pathogens. This chapter outlines the anatomy relevant to T cell function and biology, such as antigen processing/presentation, T cell activation, and the many T cell subpopulations in the peritoneal cavity, as well as their role in cancer or other infection.
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Affiliation(s)
- Sanjay Rathod
- Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United States.
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García-Peñarrubia P, Ruiz-Alcaraz AJ, Ruiz-Ballester M, Ramírez-Pávez TN, Martínez-Esparza M. Recent insights into the characteristics and role of peritoneal macrophages from ascites of cirrhotic patients. World J Gastroenterol 2021; 27:7014-7024. [PMID: 34887625 PMCID: PMC8613641 DOI: 10.3748/wjg.v27.i41.7014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 07/02/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Macrophages are a diverse myeloid cell population involved in innate and adaptive immune responses, embryonic development, wound repair, and regulation of tissue homeostasis. These cells link the innate and adaptive immunities and are crucial in the development and sustainment of various inflammatory diseases. Macrophages are tissue-resident cells in steady-state conditions; however, they are also recruited from blood monocytes after local pathogen invasion or tissue injury. Peritoneal macrophages vary based on their cell complexity, phenotype, and functional capabilities. These cells regulate inflammation and control bacterial infections in the ascites of decompensated cirrhotic patients. Our recent work reported several phenotypic and functional characteristics of these cells under both healthy and pathological conditions. A direct association between cell size, CD14/CD16 expression, intracellular level of GATA-6, and expression of CD206 and HLA-DR activation/maturation markers, indicate that the large peritoneal macrophage CD14highCD16high subset constitutes the mature phenotype of human resident peritoneal macrophages during homeostasis. Moreover, elevated expression of CD14/CD16 is related to the phagocytic capacity. The novel large CD14highCD16high peritoneal subpopulation is increased in the ascites of cirrhotic patients and is highly sensitive to lipopolysaccharide (LPS)-induced activation, thereby exhibiting features of inflammatory priming. Thus, phosphorylation of ERK1/2, PKB/Akt, and c-Jun is remarkably increased in response to LPS in vitro, whereas that of p38 MAPK is reduced compared with the monocyte-derived macrophages from the blood of healthy controls. Furthermore, in vitro activated monocyte-derived macrophages from ascites of cirrhotic patients secreted significantly higher levels of IL-6, IL-10, and TNF-α and lower amounts of IL-1β and IL-12 than the corresponding cells from healthy donor’s blood. Based on these results, other authors have recently reported that the surface expression level of CD206 can be used to identify mature, resident, inflammatory peritoneal macrophages in patients with cirrhosis. Soluble CD206 is released from activated large peritoneal macrophages, and increased concentrations in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) indicate reduced odds of survival for 90 d. Hence, the level of soluble CD206 in ascites might be used to identify patients with SBP at risk of death. In conclusion, peritoneal macrophages present in ascites of cirrhotic patients display multiple phenotypic modifications characterized by reduced ratio of cells expressing several membrane markers, together with an increase in the ratios of complex and intermediate subpopulations and a decrease in the classic-like subset. These modifications may lead to the identification of novel pharmaceutical targets for prevention and treatment of hepatic damage.
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Affiliation(s)
- Pilar García-Peñarrubia
- Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, Murcia 30100, Spain
| | - Antonio José Ruiz-Alcaraz
- Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, Murcia 30100, Spain
| | - Miriam Ruiz-Ballester
- Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, Murcia 30100, Spain
| | - Tamara Nadira Ramírez-Pávez
- Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, Murcia 30100, Spain
| | - María Martínez-Esparza
- Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, Murcia 30100, Spain
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Ramírez-Pavez TN, Martínez-Esparza M, Ruiz-Alcaraz AJ, Marín-Sánchez P, Machado-Linde F, García-Peñarrubia P. The Role of Peritoneal Macrophages in Endometriosis. Int J Mol Sci 2021; 22:ijms221910792. [PMID: 34639133 PMCID: PMC8509388 DOI: 10.3390/ijms221910792] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 02/06/2023] Open
Abstract
Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into the abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, the presence of immune dysregulation occupies a prominent place, pointing out the beneficial and harmful outcomes of macrophages in the pathogenesis of this disease. Macrophages are tissue-resident cells that connect innate and adaptive immunity, playing a key role in maintaining local homeostasis in healthy conditions and being critical in the development and sustainment of many inflammatory diseases. Macrophages accumulate in the peritoneal cavity of women with endometriosis, but their ability to clear migrated endometrial fragments seems to be inefficient. Hence, the characteristics of the peritoneal immune system in endometriosis must be further studied to facilitate the search for new diagnostic and therapeutic tools. In this review, we summarize recent relevant advances obtained in both mouse, as the main animal model used to study endometriosis, and human, focusing on peritoneal macrophages obtained from endometriotic patients and healthy donors, under the perspective of its future clinical translation to the role that these cells play on this pathology.
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Affiliation(s)
- Tamara N. Ramírez-Pavez
- Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain; (T.N.R.-P.); (M.M.-E.); (A.J.R.-A.)
| | - María Martínez-Esparza
- Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain; (T.N.R.-P.); (M.M.-E.); (A.J.R.-A.)
| | - Antonio J. Ruiz-Alcaraz
- Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain; (T.N.R.-P.); (M.M.-E.); (A.J.R.-A.)
| | - Pilar Marín-Sánchez
- Servicio de Ginecología y Obstetricia, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, 30120 Murcia, Spain;
| | - Francisco Machado-Linde
- Servicio de Ginecología y Obstetricia, Hospital Clínico Universitario Reina Sofía, CARM, 30002 Murcia, Spain;
| | - Pilar García-Peñarrubia
- Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain; (T.N.R.-P.); (M.M.-E.); (A.J.R.-A.)
- Correspondence: ; Tel.: +34-8-6888-4673
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Balzer MS, Helmke A, Ackermann M, Casper J, Dong L, Hiss M, Kiyan Y, Rong S, Timrott K, von Vietinghoff S, Wang L, Haller H, Shushakova N. Protein kinase C beta deficiency increases glucose-mediated peritoneal damage via M1 macrophage polarization and up-regulation of mesothelial protein kinase C alpha. Nephrol Dial Transplant 2020; 34:947-960. [PMID: 30247663 DOI: 10.1093/ndt/gfy282] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Peritoneal membrane (PM) damage during peritoneal dialysis (PD) is mediated largely by high glucose (HG)-induced pro-inflammatory and neo-angiogenic processes, resulting in PM fibrosis and ultrafiltration failure. We recently demonstrated a crucial role for protein kinase C (PKC) isoform α in mesothelial cells. METHODS In this study we investigate the role of PKCβ in PM damage in vitro using primary mouse peritoneal macrophages (MPMΦ), human macrophages (HMΦ) and immortalized mouse peritoneal mesothelial cells (MPMCs), as well as in vivo using a chronic PD mouse model. RESULTS We demonstrate that PKCβ is the predominant classical PKC isoform expressed in primary MPMΦ and its expression is up-regulated in vitro under HG conditions. After in vitro lipopolysaccharides stimulation PKCβ-/- MPMΦ demonstrates increased levels of interleukin 6 (IL-6), tumour necrosis factor α, and monocyte chemoattractant protein-1 and drastically decrease IL-10 release compared with wild-type (WT) cells. In vivo, catheter-delivered treatment with HG PD fluid for 5 weeks induces PKCβ up-regulation in omentum of WT mice and results in inflammatory response and PM damage characterized by fibrosis and neo-angiogenesis. In comparison to WT mice, all pathological changes are strongly aggravated in PKCβ-/- animals. Underlying molecular mechanisms involve a pro-inflammatory M1 polarization shift of MPMΦ and up-regulation of PKCα in MPMCs of PKCβ-/- mice. Finally, we demonstrate PKCβ involvement in HG-induced polarization processes in HMΦ. CONCLUSIONS PKCβ as the dominant PKC isoform in MPMΦ is up-regulated by HG PD fluid and exerts anti-inflammatory effects during PD through regulation of MPMΦ M1/M2 polarization and control of the dominant mesothelial PKC isoform α.
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Affiliation(s)
- Michael S Balzer
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Alexandra Helmke
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Martina Ackermann
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.,Phenos, Hannover, Germany
| | - Janis Casper
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Lei Dong
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Marcus Hiss
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Yulia Kiyan
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Song Rong
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Kai Timrott
- Department for General, Abdominal and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | | | - Le Wang
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.,Department of Nephrology, Tongji Medical College, Wuhan, China
| | - Hermann Haller
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Nelli Shushakova
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.,Phenos, Hannover, Germany
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Brulez HF, Verbrugh HA. First -Line Defense Mechanisms in the Peritoneal Cavity during Peritoneal Dialysis. Perit Dial Int 2020. [DOI: 10.1177/089686089501507s04] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Harald F.H. Brulez
- Department of Nephrology, Academic Hospital of the Academic Hospital Vrije Universiteit
| | - Henri A. Verbrugh
- Amsterdam,. Department of Clinical Microbiology, University Hospital “Dijkzigt,” Erasmus University of Rotterdam, The Netherlands
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7
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De Castro MF, Selgas R, Jimenez C, Baja MA, Martinez V, Romero JR, De Alvaro F, Vara F. Cell Populations Present in the Nocturnal Peritoneal Effluent of Patients on Continuous Ambulatory Peritoneal Dialysis and Their Relationship with Peritoneal Function and Incidence of Peritonitis. Perit Dial Int 2020. [DOI: 10.1177/089686089401400313] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective To study the relationship between peritoneal effluent cells and infection rate and to relate this population with functional characteristics. Design Prospective, longitudinal, and comparative study. Setting Outpatient continuous ambulatory peritoneal dialysis (CAPD) unit of a university medical center. Participants Seventy-one uninfected patients, treated for 0-156 months on CAPD, in stable condition were studied (33 female, 38 male). Interventions Nocturnal peritoneal effluent (NPE) was drained with EDT A (2.5 mmol/L) at 37°C and centrifuged at 2500 rpm for 9 minutes. Measurements Accumulated peritoneal inflammation days/year and ultrafiltration/diffusion (mass transfer coefficients (MTCs) for small molecules) capacities were recorded. Cellular count (cells/night) was performed using a Neubauer chamber. Macrophage function was assessed by cytochemical (lysosomal enzyme content: ANAE, beta-glucuronidase, acid phosphatase) and immunohistochemical procedures (expression of membrane antigens, CD4, 11b, 11c, 14,16,25,35, and 71). Results The macrophage is the most frequently appearing cell in the NPE. Cell count decreases over time on CAPD (from 20 x 106 to 5 x 106 after the first year). Intrapatient variability was low, but interpatient differences were marked. Mesothelial cell count remained stable over time (0.25 0.5 x 106). Four of our patients showed a “transforming” change in these cells. Previous incidence of peritonitis and values of functional measurements did not correlate with cell count or expressions of macrophage function (lysosome enzyme content and percentage of cells expressing different membrane antigens). Conclusion There is difficulty interpreting the results on peritoneal effluent cells and their relationship with the incidence of peritonitis and functional characteristics of the peritoneum. No definite conclusions can be drawn other than the great interpatient and intrapatient variability. The presence of abnormal peritoneal cells with undetermined origin and function suggests the need for periodic studies of peritoneal effluent cells on long-term CAPD patients.
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Affiliation(s)
| | - Rafael Selgas
- Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Spain
| | - Carlos Jimenez
- Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Spain
| | | | - Victoria Martinez
- Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Spain
| | - Jose Ramon Romero
- Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Spain
| | - Fernando De Alvaro
- Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Spain
| | - Francisco Vara
- Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Spain
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8
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Affiliation(s)
- Nicholas Topley
- Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Cardiff, United Kingdom
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9
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Phagocytosis and Killing of Suspended and Adhered Bacteria by Peritoneal Cells after Dialysis. Perit Dial Int 2020. [DOI: 10.1177/089686089501500407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective To determine the effect of dialysis fluid containing various glucose concentrations on the phagocytosis and killing of Staphylococcus aureus by rat peritoneal cells under conditions mimicking the in vivo situation. Design Phagocytosis and killing were evaluated by quantitation of the killing capacity of macrophages after in vivo phagocytosis of the bacteria as well as by an in vitro flow cytometric assay of the phagocytosis and killing of adhered bacteria by peritoneal cells. Animals Male Wistar rats. Main Outcome Measure It was expected that the intraperitoneal administration of dialysis fluid would im pair the capacity of peritoneal cells to eliminate bacteria. Results The first test revealed no effects of glucose concentration or dwell time on the killing of phagocytosed bacteria by macrophages, median percentages ranging between 29% and 64%. In the second series of experiments no effect of glucose concentration on the phagocytosis and killing of adhered bacteria was found either; however, longer dwell times significantly enhanced both the phagocytosis (at a dwell time of 1 hour, under 20%; at dwell times of 4 or 18 hours, above 20%, p < 0.02) and the killing (at a dwell time of 1 hour, under 53%; at dwell times of 4 and 18 hours, above 70%, p < 0.01). Conclusions Glucose concentration has no effect on the phagocytosis and killing of Staphylococcus aureus, whereas the dwell time significantly enhances both of these functional capacities of peritoneal cells if the bacteria are adhered to surfaces.
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10
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Lamperi S, Carozzi S. Defective Opsonic Activity of Peritoneal Effluent during Continuous Ambulatory Peritoneal Dialysis (CAPD): Importance and Prevention. Perit Dial Int 2020. [DOI: 10.1177/089686088600600211] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
To evaluate peritoneal immunological defenses and to find a way to prevent peritonitis we have studied the capacity of peritoneal dialysis effluent (PDE) to opsonize bacteria, and the phagocytic activity of peritoneal macrophages (PM). The subjects were 40 uremic patients followed for a mean period of 36 months and 40 normal women who underwent laparoscopy (controls). Opsonic capacity for Staphylococcus epidermidis of undiluted PDE from CAPD patients with low peritonitis incidence (LPI) proved to be similar to that of 10% control serum. However, the capacity of effluent from patients with a high peritonitis incidence (HPI) was noticeably inferior. In these cases, IgG concentration in PDE was lower than in LPI patients. There was a significant correlation between opsonization capacity for bacteria and IgG concentration values in PDE. We found inverse correlations between opsonic capacity of PDE and number of episodes of peritonitis. Phagocytic capacity of PM from CAPD patients was similar to that of control PM when micro-organisms were preopsonized by control serum. Treatment with intraperitoneal intmunoglobulin raised PDE opsonization capacity and lowered the incidence in those with previous HPI, thus demonstrating the importance of abnormal opsonization in CAPD peritonitis and the possibility of preventing infection by prophylaxis with intraperitoneal immunoglobulin. Intravenous immunoglobulin does not reduce the incidence of infection.
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Affiliation(s)
| | - Silvia Carozzi
- Nephrology Department, St. Martin Hospital, Genoa, Italy
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11
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Bog HJ, Vlaanderen K, Van Der Meulen J, De Veld JC, Oe LP, Beelen RHJ. Peritoneal Macrophages in Short Dwell Time Effluent Show Diminished Phagocytosis. Perit Dial Int 2020. [DOI: 10.1177/089686088800800305] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We investigated the effect of different i.p. dwell times of dialysis fluid on the composition and phagocytic capacity of the peritoneal cells. We examined dialysate after 1.5 and 15 h dwell time in 10 continuous cyclic peritoneal dialysis (CCPD) patients and after 8 h dwell time in 14 continuous ambulatory peritoneal dialysis (CAPD) patients. There was no significant difference in viability, composition, and Fc receptor positive cells among the peritoneal cells in the studied effluents of CCPD and CAPD patients. However, the yield of peritoneal cells and the phagocytic capacity of IgG-coated sheep red blood cells ([lgG]SRBC) by peritoneal macro phages in 1.5 h dwell time dialysate was significantly decreased when compared with 15 h dwell time dialysates. In addition, the total phagocytic capacity of peritoneal cells in 1.5 h dwell time dialysate is dramatically decreased when compared with the 15 h dwell time dialysate and 8 h dwell time dialysate of CAPD patients. These findings must be taken in consideration by performing three rapid exchanges after the diagnosis of a peritonitis.
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Affiliation(s)
- Harm J. Bog
- Departments of Cell Biology, Medical Faculty and University Hospital, Free University, Amsterdam, The Netherlands
| | - Klaag Vlaanderen
- Departments of Nephrology, Medical Faculty and University Hospital, Free University, Amsterdam, The Netherlands
| | - Jan Van Der Meulen
- Departments of Nephrology, Medical Faculty and University Hospital, Free University, Amsterdam, The Netherlands
| | - Jog C. De Veld
- Departments of Cell Biology, Medical Faculty and University Hospital, Free University, Amsterdam, The Netherlands
| | - Liem P. Oe
- Departments of Nephrology, Medical Faculty and University Hospital, Free University, Amsterdam, The Netherlands
| | - Robert H. J. Beelen
- Departments of Haemotology, Medical Faculty and University Hospital, Free University, Amsterdam, The Netherlands
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12
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13
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Interleukin-10, Interferon Gamma, Interleukin-2, and Soluble Interleukin-2 Receptor Alpha Detected during Peritonitis in the Dialysate and Serum of Patients on Continuous Ambulatory Peritoneal Dialysis. Perit Dial Int 2020. [DOI: 10.1177/089686089601600610] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective To analyze interleukin (IL)-10, interferon gamma (IFN-y), IL-2, and soluble IL-2 receptor alpha (sIL2Rα) in the dialysate and serum of patients on continuous ambulatory peritoneal dialysis (CAPD). Design and Patients Samples from dialysate bags were collected during the initial month of dialysis. During peritonitis, samples were collected from the first three bags on the day of admittance to the hospital and from the night bags on days 3 and 10. Serum samples were drawn on days 1 and 10. .Results: IL-10 was detected in all dialysate samples except one on the first day of infection, with a peak median level of 50 pg/mL and a slow decrease thereafter. In serum the median levels never exceeded detectable levels. Patients infected with Escherichia coli or Staphylococcus aureus had higher IL-10 levels in dialysate on day 3 as compared to the remaining patients (p < 0.05). If the catheter had to be drawn, because of persistent cloudy dialysate, the IL-10 levels remained elevated for a longer time (p<0.05). IFN-y and IL-2were detected only in the dialysate of patients infected with either S. aureusor S. epidermidis. Only one serum sample showed increased IFN-y. SIL-2Rα was found in all the serum and dialysis samples from the first day of infection. Contrary to the analyzed cytokines, the receptor showed several fold higher levels in serum as compared to the dialysate. During the infection the receptor levels in the dialysate increased, while they remained stationary in the serum, indicating a local production. Conclusion This is the first time IL-10 has been demonstrated in the dialysate during peritonitis in CAPD patients. In view of its role as a suppressor of the immune and inflammatory responses, it is a potentially important observation, which might have clinical implications in the future.
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14
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Mortier S, Lameire NH, De Vriese AS. The Effects of Peritoneal Dialysis Solutions on Peritoneal Host Defense. Perit Dial Int 2020. [DOI: 10.1177/089686080402400203] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Conventional peritoneal dialysis fluid (PDF) is a bioincompatible solution owing to the acidic pH, the high glucose concentrations and the associated hyperosmolarity, the high lactate concentrations, and the presence of glucose degradation products (GDPs). This unphysiologic composition adversely affects peritoneal host defense and may thus contribute to the development of PD-related peritonitis. The viability of polymorphonuclear leukocytes, monocytes, peritoneal macrophages, and mesothelial cells is severely depressed in the presence of conventional PDF. In addition, the production of inflammatory cytokines and chemoattractants by these cells is markedly affected by conventional PDF. Further, conventional PDF hampers the recruitment of circulating leukocytes in response to an infectious stimulus. Finally, phagocytosis, respiratory burst, and bacterial killing are markedly lower when polymorphonuclear leukocytes, monocytes, and peritoneal macrophages are exposed to conventional PDF. Although there are a few discrepant results, all major PDF components have been implicated as causative factors. Generally, novel PDF with alternative osmotic agents or with alternative buffers, neutral pH, and low GDP content have much milder inhibitory effects on peritoneal host defense. Clinical studies, however, still need to demonstrate their superiority with respect to the incidence of PD-related peritonitis.
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15
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Lewis S, Holmes C. Host Defense Mechanisms in the Peritoneal Cavity of Continuous Ambulatory Peritoneal Dialysis Patients: First of Two Parts. Perit Dial Int 2020. [DOI: 10.1177/089686089101100105] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
This article provides a review of studies on peritoneal white blood cells (WBC) in CAPD patients. To some extent these studies support the concept that the peritoneal cavity of these patients contains adequate-functioning WBC that can provide effective antimicrobial defenses when they are studied in dialysate-free media. Commercially available dialysis solutions significantly impair WBC function. In some patients with high incidences of peritonitis, there appears to be reduced bactericidal capacity of their peritoneal macrophages. CAPD seems to contribute to a state of both macrophage and lymphocyte activation in the peritoneal cavity. The clinical consequences of this chronic activation are not known.
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Affiliation(s)
- Sharon Lewis
- Department of Pathology, BRF #323, University of New Mexico, School of Medicine, Albuquerque, NM
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16
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Affiliation(s)
- Fu Keung Li
- Division of Nephrology; University Department of Medicine, Queen Mary Hospital, Hong Kong, China
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17
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Topley N, Mackenzie R, Jörres A, Goles GA, Davies M, Williams JD. Cytokine Networks in Continuous Ambulatory Peritoneal Dialysis: Interactions of Resident Cells during Inflammation in the Peritoneal Cavity. Perit Dial Int 2020. [DOI: 10.1177/089686089301302s71] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Nicholas Topley
- Universitätsklinikum Rudolf Virchow, Charlottenburg-Berlin, Germany
| | - Ruth Mackenzie
- Universitätsklinikum Rudolf Virchow, Charlottenburg-Berlin, Germany
| | - Achim Jörres
- Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Cardiff, U.K., and Abteilung for Innere Medizin mit Schwerpunkt Nephrologie, Germany
| | - Gerald A. Goles
- Universitätsklinikum Rudolf Virchow, Charlottenburg-Berlin, Germany
| | - Malcolm Davies
- Universitätsklinikum Rudolf Virchow, Charlottenburg-Berlin, Germany
| | - John D. Williams
- Universitätsklinikum Rudolf Virchow, Charlottenburg-Berlin, Germany
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18
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Sulowicz W, Cichocki T, Hanicki Z. Changes in Activity of Selected Lysosomal Enzymes in Peritoneal Macrophages of Renal Failure Patients on Peritoneal Dialysis. Perit Dial Int 2020. [DOI: 10.1177/089686088900900417] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Activity of acid phosphatase (AP), beta-glucuronidase (GR), N-acetyl-beta-D-glucosaminidase (GZ), and peroxidase (P) was assessed using a semiquantitative cytochemical method in peritoneal macro phages of 30 patients with end-stage renal failure treated by intermittent peritoneal dialysis and of 30 control patients with normal renal function. The dialysed patients showed a significantly higher activity of GR and P at the beginning of the treatment as compared with the respective activities observed in the control group and a further significant rise of these activities after 4 months of dialysis. Activity of AP at the beginning of the treatment was insignificantly lower than in the control group and the difference became significant at the end of the investigated period. There was no significant difference between the dialysed patients and the control group in the activity of GZ assessed at the beginning of the dialytic treatment and after 4 months of dialysis. A significant decrease in that activity was, however, observed in the course of dialysis.
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Affiliation(s)
- Wladyslaw Sulowicz
- Department of Nephrology and Department of Histology, Medical Academy, Krakow, Poland
| | - Tadeusz Cichocki
- Department of Nephrology and Department of Histology, Medical Academy, Krakow, Poland
| | - Zygmunt Hanicki
- Department of Nephrology and Department of Histology, Medical Academy, Krakow, Poland
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19
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Sulowicz W, Hanicki Z, Chichocki T, Zembala M, Ruggiero I, Uracz W. Functional Characteristics of Peritoneal Macrophages of Renal Failure Patients on Peritoneal Dialysis. Perit Dial Int 2020. [DOI: 10.1177/089686089101100313] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Functional activity of peritoneal macrophages of 50 patients with end-stage renal failure on intermittent peritoneal dialysis (IPD) and of 30 control subjects with normal renal function was determined. Phagocytosis of latex particles by macrophages of dialyzed patients was significantly lower as compared with the controls. Further depression of the phagocytic activity was observed during bacterial peritonitis. Macrophages from the dialyzed patients also showed nonsignificantly decreased functional expression of Fc receptors (FcR) and increased spontaneous nitro blue tetrazolium (NeT) reduction.
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Affiliation(s)
- Wladyslaw Sulowicz
- Department of Nephrology, Nicolaus Copernicus University School of Medicine, Cracow, Poland
| | - Zygmunt Hanicki
- Department of Nephrology, Nicolaus Copernicus University School of Medicine, Cracow, Poland
| | - Tadeusz Chichocki
- Department of Histology, Nicolaus Copernicus University School of Medicine, Cracow, Poland
| | - Marek Zembala
- Department of ClinicalImmunology, Nicolaus Copernicus University School of Medicine, Cracow, Poland
| | - Irena Ruggiero
- Department of ClinicalImmunology, Nicolaus Copernicus University School of Medicine, Cracow, Poland
| | - Wojciech Uracz
- Department of ClinicalImmunology, Nicolaus Copernicus University School of Medicine, Cracow, Poland
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20
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Usbe M, Gazzo RM, Mile M, Brazzo A, Zuc F, Depet G, Brag B, Los R. Treatment of Acute Peritonitis by Temporary Discontinuation of Dialysis and Low Doses of Oral Ciprofloxacin in Patients on Capd. ARCH ESP UROL 2020. [DOI: 10.1177/089686089401400220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Mario Usbe
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Rosa M. Gazzo
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Maurizio Mile
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Alessandra Brazzo
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Francesco Zuc
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Giorgio Depet
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Barbara Brag
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
| | - Renata Los
- Servizio di N efrologia e Dialisi Ospedale di Leno Servizio di Nefrologia e Dialisi Ospedale di Crema Italy
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21
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Abstract
This review outlines the problems involved in assessing the biocompatibility of PD fluids. It has summarized the data available from conventional in vitro studies and highlights many of the inadequacies of this approach. In viva data are lacking both on host defense and on the clinical effect of changing conven tional PD fluids for a more “ideal” formulation. The best parameters for assessing biocompatibility need to be defined. Alternative formulation of fluids must be aimed towards (1) a system that interferes minimally with host defense, and (2) a system that maintains the integrity of the peritoneal membrane for ultrafiltration and clearance. Cell culture studies should be designed to model the in viva situation. Ex viva studies (cells exposed within the peritoneal cavity) should be used to support in viva findings. Finally, in vitra results must be related to clinical significance, and changes in fluid composition should be followed by improvements in clinical outcome.
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Affiliation(s)
- Nicholas Topley
- Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Wales, United Kingdom
| | - Gerald A. Goles
- Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Wales, United Kingdom
| | - John D. Williams
- Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, Wales, United Kingdom
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22
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Ejlersen E, Brandi L, Løkkegaard H, Ladefoged J, Kopp R, Haarh P. Is Initial (24 Hours) Lavage Necessary in Treatment of CAPD Peritonitis? Perit Dial Int 2020. [DOI: 10.1177/089686089101100109] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
A randomized trial was conducted to examine the influence of initiallavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty -six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including either initial24 hours lavage before resumption of routine CAPD schedule (prior standard approach) or continued prolonged exchanges as in routine CAPD schedule. Median time to solved infection (normalization of white cell count in dialysis effluent) was identical (3 days) in the two groups. Treatment success rate was found to be 72% in the group with initial lavage and 89% in the group with prolonged exchanges. The difference in treatment success (17%) in favour of continued CAPD schedule was not found significant (95% confidence limits −1% to 35%). The results suggest lavage to be of no clinical benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock.
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Affiliation(s)
- Ellen Ejlersen
- Medical Department B, Division of Nephrology, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark
| | - Lisbet Brandi
- Medical Department P, Division of Nephrology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark, and the Danish Study Groul J on Peritonitis in Dialvsis (DASPID)
| | - Hans Løkkegaard
- Medical Department B, Division of Nephrology, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark
| | - Jørgen Ladefoged
- Medical Department P, Division of Nephrology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark, and the Danish Study Groul J on Peritonitis in Dialvsis (DASPID)
| | - Rena Kopp
- Medical Department B, Division of Nephrology, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark
| | - Pia Haarh
- Medical Department P, Division of Nephrology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark, and the Danish Study Groul J on Peritonitis in Dialvsis (DASPID)
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23
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Jörres A, Gahl GM, Frei U. In Vitro Studies on the Effect of Dialysis Solutions on Peritoneal Leukocytes. Perit Dial Int 2020. [DOI: 10.1177/089686089501507s06] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Achim Jörres
- Abteilung für Innere Medizin mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Virchow-Klinikum, Berlin, Germany
| | - Gerhard M. Gahl
- Abteilung für Innere Medizin mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Virchow-Klinikum, Berlin, Germany
| | - Ulrich Frei
- Abteilung für Innere Medizin mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Virchow-Klinikum, Berlin, Germany
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24
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Selgas R, De Castro MF, Viguer JM, Burgos E, Bajo MA, Carcamo C, Vara F. Transformed Mesothelial Cells in Patients on CAPD for Medium to Long Term Periods. Perit Dial Int 2020. [DOI: 10.1177/089686089501500405] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective To describe the characteristics of abnormal cells present in the peritoneal effluent of 4 continuous ambulatory peritoneal dialysis (CAPD) patients; the cells were accidentally detected in a longitudinal study of cell populations in 83 patients. Design Descriptive study. Participants Four stable CAPD patients (2 male, 2 female). Interventions Peritoneal cells were collected from nocturnal peritoneal effluent (NPE) by centrifugation. Measurements Light microscopy, ultrastructural, cytochemical, and immunohistochemical characteristics were studied. Results The abnormal cells were characterized by a flat appearance, large size (diameter 100 μm) -six to ten times larger than a normal macrophage, a broad acidophilic cytoplasm with rare granulations, and a low nucleus/cytoplasm ratio. The nucleus was pyknotic, with dense chromatin and sometimes appeared fragmented. Its number presented a considerable variability between the patients and was much higher in the 2 females. This number remained stable in each patient over time. These cells were negative for betaglucuronidase and positive for PAS stain with variable intensity. A very low number of flat cells were positive for vimentin with weak intensity, whereas cytokeratin and epithelial membrane antigen (EMA) were positive in a higher number of cells with medium to strong intensity. Ultrastructural studies showed numerous short surface microvilli, cytoplasm well-developed with intracytoplasmic lumina and abundant, dispersed intermediate filaments, scattered mitochondria, and stacks of rough endoplasmic reticulum were observed. Dispersed secretory vacuoles and isolated lipid vacuoles were present. Conclusion All these features imply that they are mesothelial in origin and are suggestive of a change known as peritoneal squamous metaplasia. To date, the clinical follow-up of our patients has shown a benign outcome; further studies are necessary to elucidate the significance of this peritoneal squamous metaplasia in CAPD patients.
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Affiliation(s)
| | | | | | - Emilio Burgos
- Pathology Departments, Universidad Autonoma, Madrid, Spain
| | | | | | - Francisco Vara
- Hospital La Paz; Biochemistry Department, Universidad Autonoma, Madrid, Spain
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25
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Lewis SL, Kutvirt SG, Cooper CL, Bonner PN, Holmes CJ. Characteristics of Peripheral and Peritoneal Lymphocytes from Continuous Ambulatory Peritoneal Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686089301302s69] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The role of peritoneal lymphocytes in host immunity for continuous ambulatory peritoneal dialysis (CAPD) patients Is just beginning to be understood. CAPD therapy Increases the proportion of peritoneal lymphocytes, most of which demonstrate signs of activation. There are decreased peritoneal T cells and increased peritoneal B cells as compared to the patients’ peripheral blood. When studies examine Immunophenotypes of peripheral and peritoneallymphocytes over time, no significant changes are found. Although changes in peritoneal lymphocyte subsets occur during peritonitis episodes, there are no changes In peripheral blood lymphocytes. The purpose of this article Is to provide a brief review of research that has studied lymphocytes In CAPD patients.
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Affiliation(s)
- Sharon L. Lewis
- Department of Pathology; University of New Mexico, Albuquerque, U.S.A
| | - Susan G. Kutvirt
- Department of Pathology; University of New Mexico, Albuquerque, U.S.A
| | - Christa L. Cooper
- Department of Pathology; University of New Mexico, Albuquerque, U.S.A
| | - Peter N. Bonner
- New Mexico, University of Phoenix, Albuquerque, New Mexico, Illinois, U.S.A
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26
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Longitudinal Study of Peritoneal Defence Mechanisms in Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD). Perit Dial Int 2020. [DOI: 10.1177/089686088900900208] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Peritoneal cellular and humoral defence mechanisms have been examined in a group of 16 patients over a nine-month period from the day of commencement of continuous ambulatory peritoneal dialysis (CAPD). Significant decreases in the levels of IgG, C3, and opsonic activity occurred with the passage of time in the overnight peritoneal dialysis effluent (PDE). The ability of PDE to inhibit in vitro growth of Staphylococcus epidermidis also decreased. The number ot cells in the PDE and their ability to kill S. epidermidis decreased, although there was no significant change in their ability to ingest this organism. These results suggest that the immunological protection of the peritoneal cavity decreases with time, and this may account for the increase in the incidence of peritonitis with length of time on CAPD that some workers have reported.
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27
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Brauner A, Hertting O, Alkstrand E, Sandberg E, Chromek M, Chen ZW, Östenson CG. Capd Peritonitis Induces the Production of a Novel Peptide, Daintain/Allograft Inflammatory Factor-1. Perit Dial Int 2020. [DOI: 10.1177/089686080302300101] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
← Objectives To study the occurrence of a novel macrophage-derived peptide, daintain/allograft inflammatory factor-1 (AIF-1), in dialysate from continuous ambulatory peritoneal dialysis (CAPD) patients at commencement and after a follow-up period of therapy and during peritonitis. In addition, we studied peptide production in response to bacterial stimulation of monocytes and macrophages. ← Design Peritoneal fluid and supernatants from cells stimulated with different bacteria were analyzed for daintain/AIF-1. ← Patients and Setting Peritoneal fluid was obtained from 5 patients at commencement of CAPD therapy and during 8 weeks follow-up, and from 14 patients (10 males, 4 females) during CAPD peritonitis and during the noninfected steady state. All patients were admitted to the Karolinska Hospital. A human monocyte cell-line, THP-1 was differentiated to macrophages, and both monocytes and macrophages were stimulated with live and heat-inactivated Escherichia coli, Staphylococcus aureus, and S. epidermidis Cells were also stimulated with interleukin (IL)-1β and interferon gamma (IFNγ). Daintain/AIF-1 was analyzed with radioimmunoassay technique and IL-8 with enzyme immunoassay technique. ← Results An increased production of daintain/AIF-1 was observed in the first spent dialysate in the newly started CAPD patients, with a decrease during the follow-up period ( p < 0.05). During peritonitis, the first spent dialysate revealed significantly higher levels of daintain/AIF-1 (3.9 ng/mL) compared to the noninfected state (0.8 ng/mL), with production normalizing after 9 – 12 days. Bacterial stimulation with E. coli, S. aureus or S. epidermidi sinduced higher daintain/AIF-1 response in monocytes compared to macrophages ( p < 0.05). Live bacteria induced higher production of the peptide compared to heat-inactivated bacteria ( p < 0.05). Interleukin-1β and IFNγ were used to stimulate monocytes and macrophages; however, no daintain/AIF-1 production was found, although increased IL-8 levels were detected. ← Conclusion CAPD peritonitis induces a high and prominent daintain/AIF-1 response. Bacteria are able to induce a response of the peptide from monocytes and macrophages, and it is likely that the virulent parts of the bacteria are heat-labile structures. The early rise in daintain/AIF-1 might be used as a marker of CAPD peritonitis.
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Affiliation(s)
- Annelie Brauner
- Departments of Clinical Microbiology and MTC, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Olof Hertting
- Departments of Clinical Microbiology and MTC, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Eva Alkstrand
- Departments of Clinical Microbiology and MTC, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Elvi Sandberg
- Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital, Stockholm, Sweden
| | - Milan Chromek
- Departments of Clinical Microbiology and MTC, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Zheng-Wang Chen
- Department of Biochemistry, Karolinska Institute, Stockholm, Sweden
| | - Claes-Göran Östenson
- Departments of Clinical Microbiology and MTC, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
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28
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Dadfar E, Lundahl J, Fernvik E, Nopp A, Hylander B, Jacobson SH. Leukocyte CD11b and CD62L Expression in Response to Interstitial Inflammation in CAPD Patients. Perit Dial Int 2020. [DOI: 10.1177/089686080402400103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective Very little is known about the kinetics of leukocyte recruitment and the modulation of adhesion molecules on leukocytes in the interstitium at the site of inflammation outside the peritoneal cavity in patients on peritoneal dialysis. These issues were addressed in the present study. Patients and Methods Two skin blisters were raised in 10 patients on peritoneal dialysis and in 19 healthy subjects. After 12 hours, blister exudates were collected and the blisters were thereafter challenged with buffer or autologous serum in order to establish an intermediate and an intense cutaneous inflammation. Leukocyte count, leukocyte CD11b/CD62L expression, monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were determined in blood and at the three sites of interstitial inflammation by immunostaining, flow cytometry, and ELISA. Results In monocytes and granulocytes, expression of CD11b increased and CD62L decreased significantly during the transmigration process from the peripheral blood into the three sites of interstitial inflammation. In the nonstimulated blister, expression of CD11b on both monocytes and granulocytes was similar in patients and healthy subjects. At the site of intermediate inflammation, expression of CD11b on both monocytes and granulocytes was significantly higher in healthy subjects compared to patients ( p < 0.05 and p < 0.001 respectively). At the site of intense inflammation, expression of CD11b on granulocytes was significantly lower ( p < 0.001), and CD62L significantly higher ( p < 0.001) in patients. Interstitial concentrations of MCP-1 and IL-8 at the sites of intermediate inflammation were significantly higher in healthy subjects compared to patients ( p < 0.05 and p < 0.05 respectively). However, at the site of intense inflammation, similar concentrations of MCP-1 and IL-8 were observed. Furthermore, there were no significant correlations between concentrations of MCP-1 and IL-8 in blister exudates and expression of CD11b on monocytes and granulocytes at the sites of interstitial inflammation. Conclusion The ability of monocytes and granulocytes to modulate the expression of adhesion molecule in response to interstitial inflammation was significantly impaired in patients on peritoneal dialysis. Furthermore, these data suggest that the expression of CD11b on leukocytes is not dependent on concentrations of IL-8 and MCP-1 in interstitium in this patient group.
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Affiliation(s)
- Elham Dadfar
- Divisions of Clinical Immunology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Joachim Lundahl
- Divisions of Clinical Immunology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Eva Fernvik
- Divisions of Clinical Immunology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Anna Nopp
- Divisions of Clinical Immunology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Britta Hylander
- Nephrology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
| | - Stefan H. Jacobson
- Nephrology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden
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29
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Glik A, Douvdevani A. T Lymphocytes: The “Cellular” Arm of Acquired Immunity in the Peritoneum. Perit Dial Int 2020. [DOI: 10.1177/089686080602600407] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
T cells are an important part of the acquired immune response and target specific antigen with their T cell receptor. The peritoneum is a special milieu within which T cells react. We describe briefly the anatomy important for T cell function. T cell biology including antigen presentation, T cell activation, and the different T cell subpopulations are reviewed. We also define innate and acquired immunity and describe the role of polymorphonuclear cells and peritoneal mesothelial cells in the regulation of leukocyte population recruitment during peritonitis. We focus particularly on peritoneal lymphocytes and compare them to the regular lymphocyte populations in the circulation. We illustrate the role of PMCs in antigen presentation and discuss the changes of CD4+ helper T cell subtypes (Th1 and Th2) during peritoneal dialysis. The role of CD8+ cytotoxic T lymphocytes and their possible destructive role for the peritoneal membrane modified by advanced glycation end products are discussed. Polymorphonuclear cells play an important role in the regulation of inflammation and immunity. We describe their possible role in supporting T cells and particularly for generating memory CD8+ T cells by secretion of interleukin-15, a potent T cell growth factor. Light is shed on γδ T cells, a special T cell population that is able to recognize antigens without the restriction of antigen presentation. We end our review with a description of regulatory T cells. This cell population is extremely important in preventing autoimmunity and in the regulation of acquired immunity.
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Affiliation(s)
- Amir Glik
- Department of Nephrology, Soroka Medical Center, and
Clinical Biochemistry Department, Faculty of Health Sciences, Ben Gurion University
of the Negev, Beer Sheva, Israel
| | - Amos Douvdevani
- Department of Nephrology, Soroka Medical Center, and
Clinical Biochemistry Department, Faculty of Health Sciences, Ben Gurion University
of the Negev, Beer Sheva, Israel
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30
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Mao R, Wang C, Zhang F, Zhao M, Liu S, Liao G, Li L, Chen Y, Cheng J, Liu J, Lu Y. Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury. J Cell Mol Med 2020; 24:3314-3327. [PMID: 32004417 PMCID: PMC7131941 DOI: 10.1111/jcmm.15005] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 12/24/2019] [Accepted: 01/06/2020] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) is a clinical condition that is associated with high morbidity and mortality. Inflammation is reported to play a key role in AKI. Although the M2 macrophages exhibit antimicrobial and anti‐inflammatory activities, their therapeutic potential has not been evaluated for AKI. This study aimed to investigate the protective effect of peritoneal M2 macrophage transplantation on AKI in mice. The macrophages were isolated from peritoneal dialysates of mice. The macrophages were induced to undergo M2 polarization using interleukin (IL)‐4/IL‐13. AKI was induced in mice by restoring the blood supply after bilateral renal artery occlusion for 30 minutes. The macrophages were injected into the renal cortex of mice. The changes in renal function, inflammation and tubular proliferation were measured. The M2 macrophages were co‐cultured with the mouse primary proximal tubular epithelial cells (PTECs) under hypoxia/reoxygenation conditions in vitro. The PTEC apoptosis and proliferation were analysed. The peritoneal M2 macrophages effectively alleviated the renal injury and inflammatory response in mice with ischaemia‐reperfusion injury (IRI) and promoted the PTEC proliferation in vivo and in vitro. These results indicated that the peritoneal M2 macrophages ameliorated AKI by decreasing inflammatory response and promoting PTEC proliferation. Hence, the peritoneal M2 macrophage transplantation can serve as a potential cell therapy for renal diseases.
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Affiliation(s)
- Ruiwen Mao
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.,West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Chengshi Wang
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Fuping Zhang
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Meng Zhao
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shuyun Liu
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Guangneng Liao
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Lan Li
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Younan Chen
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jingqiu Cheng
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jingping Liu
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yanrong Lu
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
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31
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Wong SS, Lau WY, Tse YY, Chan PK, Wan CK, Cheng YL, Yu AW. Randomized Controlled Trial on Adjunctive Lavage for Severe Peritonitis. Perit Dial Int 2019; 39:447-454. [PMID: 31337697 DOI: 10.3747/pdi.2018.00111] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 02/23/2019] [Indexed: 11/15/2022] Open
Abstract
Background:In severe peritoneal dialysis (PD)-related peritonitis, patients' response to antibiotic can be poor. We postulated that adjunctive lavage may improve the outcome in severe cases by enhancing the removal of bacteria and inflammatory cells from the peritoneum.Methods:Severe PD peritonitis was defined as poor clinical response to empirical cefazolin/ceftazidime and a PD effluent (PDE) leukocyte count > 1,090/mm3 on day 3. Enrolled patients were randomized into either the lavage group (n = 20) or control group (n = 20). In the lavage group, continuous lavage by an automated PD machine from day 3 to 5 or 6 was performed, whereas the usual PD schedule was maintained in the control group. The primary outcome was treatment success. Post hoc analysis was also performed to compare the outcome between subgroups with different severity.Results:Baseline parameters were similar in the lavage and control groups, including PDE leukocyte count on day 3 (4,871/mm3 vs 4,143/mm3, p = 0.46). Treatment success rates were high in both groups (75% vs 70%, p = 0.72). C-reactive protein (CRP) on day 3 was found to be the only predictor of treatment failure and was used to stratify all patients into tertiles of severity. Whilst a significant decline in treatment success was evident across the tertiles of increasing CRP in the control group (100% vs 85.7% vs 28.6%, p = 0.005), treatment success was relatively maintained in the lavage group (85.7% vs 71.4% vs 66.7%, p = 0.43).Conclusions:Adjunctive lavage did not improve the overall outcome, although it may be beneficial for the more severe peritonitis patients who have high CRP.
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Affiliation(s)
- Steve S Wong
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Wai-Yan Lau
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Yim-Yuk Tse
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Ping-Kwan Chan
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Ching-Kit Wan
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Yuk-Lun Cheng
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | - Alex W Yu
- Central Administration Office, Hong Kong Baptist Hospital, Hong Kong
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Cao Q, Wang Y, Wang C, Wang XM, Lee VWS, Zheng G, Zhao Y, Alexander SI, Harris DCH. Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy. Am J Physiol Renal Physiol 2018; 314:F561-F571. [PMID: 29357438 DOI: 10.1152/ajprenal.00538.2017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.
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Affiliation(s)
- Qi Cao
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Yiping Wang
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Changqi Wang
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Xin M Wang
- Flow Cytometry Facility, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Vincent W S Lee
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Guoping Zheng
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Ye Zhao
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
| | - Stephen I Alexander
- Centre for Kidney Research, Children's Hospital at Westmead , Sydney, New South Wales , Australia
| | - David C H Harris
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney , Sydney, New South Wales , Australia
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Affiliation(s)
- A. Jörres
- Nephrology, Universitätsklinikum Rudolf Virchow, Berlin-Charlottenburg - Germany
| | - N. Topley
- Institute of Nephrology, Kidney Research Unit Foundation, University of Wales College of Medicine, Royal Infirmary, Cardiff - UK
| | - G.M. Gahl
- Nephrology, Universitätsklinikum Rudolf Virchow, Berlin-Charlottenburg - Germany
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Serre A, Marie C, Beaujon G, Betail G, Cavaillon J, Deteix P. Variations of Cytokine Levels and Production in CAPD Patients. Int J Artif Organs 2018. [DOI: 10.1177/039139889702001104] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Macrophages, predominant cells in dialysates of patients on CAPD without peritonitis, produce a wide variety of substances including cytokines. The aim of this study was to examine the cytokine production in five uninfected patients. This work investigated the presence in dialysates of interleukin-1ß, interleukin-6, interleukin-8, tumor necrosis factor α and the ability of peritoneal macrophages to produce these cytokines. These results were compared with values obtained from control group in non-uremic conditions (peritoneal lavage with isotonic saline or dialysis fluid). All cytokines were detectable in dialysates. Interindividual variations in cytokine concentration in dialysates were wider than variations of production of cytokines ex vivo by stimulated and unstimulated cells. In control group, dialysis fluid inhibited the cytokine production and with isotonic saline, cells produced less cytokines than dialysis patients'cells. The highest levels of interleukin-1 and tumor necrosis factor in dialysates and the highest capacity to respond to LPS were observed in patients having the shortest duration of dialysis. The variability observed did not seem to be due to cells themselves but to their environment.
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Affiliation(s)
- A.F. Serre
- Laboratoire d'Hématologie-lmmunologie, Faculté de Pharmacie, Clermont-Ferrand
| | - C. Marie
- Laboratoire d'lmmuno-Allergie, Institut Pasteur, Paris
| | - G. Beaujon
- Laboratoire des radioisotopes in vitro, Centre Jean Perrin, Clermont-Ferrand
| | - G. Betail
- Laboratoire d'Hématologie-lmmunologie, Faculté de Pharmacie, Clermont-Ferrand
| | | | - P. Deteix
- Service de Néphrologie, Hôpital Gabriel Montpied, Clermont-Ferrand - France
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Bacchetta J, Chun RF, Gales B, Zaritsky JJ, Leroy S, Wesseling-Perry K, Boregaard N, Rastogi A, Salusky IB, Hewison M. Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation. PLoS One 2014; 9:e116530. [PMID: 25549329 PMCID: PMC4280222 DOI: 10.1371/journal.pone.0116530] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 12/08/2014] [Indexed: 12/30/2022] Open
Abstract
Patients with chronic kidney disease (CKD), who usually display low serum 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are at high risk of infection, notably those undergoing peritoneal dialysis (PD). We hypothesized that peritoneal macrophages from PD patients are an important target for vitamin D-induced antibacterial activity. Dialysate effluent fluid was obtained from 27 non-infected PD patients. Flow cytometry indicated that PD cells were mainly monocytic (37.9±17.7% cells CD14+/CD45+). Ex vivo analyses showed that PD cells treated with 25D (100 nM, 6 hrs) or 1,25D (5 nM, 6 hrs) induced mRNA for antibacterial cathelicidin (CAMP) but conversely suppressed mRNA for hepcidin (HAMP). PD cells from patients with peritonitis (n = 3) showed higher baseline expression of CAMP (18-fold±9, p<0.05) and HAMP (64-fold±7) relative to cells from non-infected patients. In 12 non-infected PD patients, oral supplementation with a single dose of vitamin D2 (100,000 IU) increased serum levels of 25D from 18±8 to 41±15 ng/ml (p = 0.002). This had no significant effect on PD cell CD14/CD45 expression, but mRNA for HAMP was suppressed significantly (0.5-fold, p = 0.04). Adjustment for PD cell CD14/CD45 expression using a mixed linear statistical model also revealed increased expression of CAMP (mRNA in PD cells and protein in effluent) in vitamin D-supplemented patients. These data show for the first time that vitamin D supplementation in vitro and in vivo promotes innate immune responses that may enhance macrophage antibacterial responses in patients undergoing PD. This highlights a potentially important function for vitamin D in preventing infection-related complications in CKD.
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Affiliation(s)
- Justine Bacchetta
- Orthopedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America
- Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
- Centre de Référence des Maladies Rénales Rares, Institut de Génomique Fonctionnelle à l’Ecole Normale Supérieure de Lyon et Université de Lyon, Lyon, France
| | - Rene F. Chun
- Orthopedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America
| | - Barbara Gales
- Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Joshua J. Zaritsky
- Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Sandrine Leroy
- Unité d’épidémiologie des maladies émergentes, Institut Pasteur, Paris, France
| | - Katherine Wesseling-Perry
- Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Niels Boregaard
- Department of Hematology, University of Copenhagen, Copenhagen, Denmark
| | - Anjay Rastogi
- Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Isidro B. Salusky
- Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Martin Hewison
- Orthopedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America
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Mitterhofer A, Umbro I, Pietropaolo V, Meçule A, Russo G, Tinti F, Fiacco F, Poli L, Bellizzi A, Anzivino E, Ferretti G, Berloco P, Chiarini F, Taliani G. Polyomavirus BK Infection in End-stage Renal Disease: Analysis of Viral Replication in Patients on Hemodialysis or Peritoneal Dialysis. Transplant Proc 2012; 44:1869-72. [DOI: 10.1016/j.transproceed.2012.06.021] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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The local inflammatory responses to infection of the peritoneal cavity in humans: their regulation by cytokines, macrophages, and other leukocytes. Mediators Inflamm 2012; 2012:976241. [PMID: 22481867 PMCID: PMC3317024 DOI: 10.1155/2012/976241] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2011] [Accepted: 11/16/2011] [Indexed: 12/22/2022] Open
Abstract
Studies on infection-induced inflammatory reactions in humans rely largely on findings in the blood compartment. Peritoneal leukocytes from patients treated with peritoneal dialysis offer a unique opportunity to study in humans the inflammatory responses taking place at the site of infection. Compared with peritoneal macrophages (pMϕ) from uninfected patients, pMϕ from infected patients display ex vivo an upregulation and downregulation of proinflammatory and anti-inflammatory mediators, respectively. Pro-IL-1β processing and secretion rather than synthesis proves to be increased in pMϕ from infectious peritonitis suggesting up-regulation of caspase-1 in vivo. A crosstalk between pMϕ, γδ T cells, and neutrophils has been found to be involved in augmented TNFα expression and production during infection. The recent finding in experimental studies that alternatively activated macrophages (Mϕ2) increase by proliferation rather than recruitment may have significant implications for the understanding and treatment of chronic inflammatory conditions such as encapsulating peritoneal sclerosis (EPS).
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Chen CY, Wu CY, Tsai TC, Lin WT, Lee WJ, Su CC, Chen HC, Chiang HC. Fas expression on peritoneal macrophages during continuous ambulatory peritoneal dialysis peritonitis. Ren Fail 2008; 30:297-301. [PMID: 18350449 DOI: 10.1080/08860220701860872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
BACKGROUND Peritonitis is a common complication of end stage renal failure (ESRF) patients receiving continuous ambulatory peritoneal dialysis (CAPD). Peritoneal macrophage may participate in the activation of specific T cells and in the generation of local cell-mediated immunity to various pathogens. The purpose of this study is to investigate the possible role of macrophage in CAPD patients with peritonitis. METHODS We evaluated the expression of Fas receptor (CD95), ICAM-1 (CD54), CD25, and CD69 by two-color flow cytometry on extravasted macrophages from 16 ESRF patients on CAPD with peritonitis (peritonitis-positive) and compared them to 11 ESRF patients on CAPD without peritonitis (peritonitis-negative) and normal controls. RESULTS We found an increased expression of CD95, CD54, and CD25 on macrophage in peritonitis-positive group compared to controls (all p < 0.001). In the peritonitis-positive group, the CD95 expression was significantly higher than that of the peritonitis-negative group (p < 0.001). The expression of CD54, CD25, and CD69, however, was not significantly different between the peritonitis-positive and peritonitis-negative CAPD subgroups. CONCLUSION We found an abnormally increased percentage of macrophage-expressing Fas receptor and ICAM-1, and the percentage of CD95+ macrophage, but not those of other markers, were increased among the subset of CAPD patients with peritonitis. The later finding suggests that this macrophage phenotype is associated with peritonitis occurring in CAPD.
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Affiliation(s)
- Chen-Yin Chen
- Division of Nephrology, Department of Medicine, Tian-Sheng Memorial Hospital, Tong-Kang, Ping-Tong, Taiwan
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Okada H, Inoue T, Kanno Y, Kobayashi T, Watanabe Y, Ban S, Neilson EG, Suzuki H. Selective depletion of fibroblasts preserves morphology and the functional integrity of peritoneum in transgenic mice with peritoneal fibrosing syndrome. Kidney Int 2004; 64:1722-32. [PMID: 14531805 DOI: 10.1046/j.1523-1755.2003.00290.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND A peritoneal fibrosing syndrome (PFS) can progressively reduce peritoneal ultrafiltration during chronic peritoneal dialysis in patients with renal failure. The pathogenesis of PFS is unclear and the role of peritoneal fibroblasts has not been evaluated experimentally. METHODS We followed the fate of fibroblasts producing PFS in a mouse model using fibroblast-specific protein 1 (FSP1) as a marker. PFS was induced by daily peritoneal infusions of chlorhexidine gluconate (CHG) saline into transgenic mice expressing the thymidine kinase (Delta tk) gene under the control of the FSP1 promoter (FSP1.Delta tk mice). To demonstrate the role of fibroblasts in PFS, we treated these FSP1.Delta tk mice with a nucleoside analogue to induce DNA chain termination and fibroblast death. RESULTS Mice receiving peritoneal infusions of CHG saline every other day for 2 weeks developed increasing numbers of FSP1+ fibroblasts in the subserosal layers of the visceral peritoneum. Mac-3+ monocytes (macrophages) subsequently accumulated over the next 2 weeks in association with increased deposition of type I collagen and increased endothelial vascularity (CD31+) in these subserosal tissues. Since these peritoneal fibroblasts expressed monocyte chemoattractant protein-1 (MCP-1), heat shock protein 47 (HSP47), and vascular endothelial growth factor (VEGF), we suspect they were partially responsible for macrophage recruitment, matrix production, and the neoangiogenesis in the subserosal tissue. Treatment of PFS in FSP1.Delta tk transgenic mice with a nucleoside analogue selectively reduced the numbers of peritoneal fibroblasts and attenuated the attendant changes in peritoneal histology. Rescuing the peritoneal membrane from chronic thickening and neoangiogenesis by reducing the number of fibroblasts also preserved ultrafiltration. CONCLUSION Peritoneal fibroblasts play a pivotal role in PFS, and their deletion using a fibroblasts-specific transgene was effective in preventing peritoneal fibrogenesis.
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Affiliation(s)
- Hirokazu Okada
- Department of Nephrology, Saitama Medical College, Saitama, Japan.
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Wang HH, Lin CY, Huang TP. Patterns of CD4/CD8 T-cell ratio in dialysis effluents predict the long-term outcome of peritonitis in patients undergoing peritoneal dialysis. Nephrol Dial Transplant 2003; 18:1181-9. [PMID: 12748353 DOI: 10.1093/ndt/gfg079] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The peritoneal immune compartment is a microenvironment with a particular T-cell repertoire and susceptible to local inflammation. To clarify the role of T lymphocytes in peritoneal immunity, the changes in T-cell subpopulations in peritoneal dialysis effluents (PDEs), and their influence on the response to the treatment of peritonitis and on its prognosis were studied in patients undergoing long-term, continuous ambulatory peritoneal dialysis (CAPD). METHODS A cohort of 36 patients treated with CAPD and who had histories of peritonitis were divided into a group with rapid and a group with delayed response to antibiotics, and were followed for 3 years. CD4/CD8 T-cell ratios, T-cell cytokine mRNA expression patterns and transforming growth factor-beta1 (TGF-beta1) concentrations were examined in PDE during bouts of peritonitis. The change in 4 h D/P creatinine during the peritoneal equilibration test (PET) between year 0 and year 3 was expressed as deltaD/P creatinine. RESULTS The serial changes in T-cell subsets in PDE during peritonitis showed two patterns: (i) pattern 1, manifest as a progressive increase in the CD4/CD8 ratio, and associated with a rapid response to treatment; and (ii) pattern 2, manifest as a progressive decrease in the CD4/CD8 ratio, and associated with a delayed response to treatment. The major T-cell phenotypes in PDE during peritonitis were Th1-CD4(+) and Tc2-CD8(+), determined by cloning techniques, RT-PCR and double immunofluorescence staining. TGF-beta1 in the effluent was undetectable in pattern 1 after 7-8 days, but remained detectable at 2 weeks in pattern 2. Pattern 2 patients had a significantly greater decrease (deltaD/P creatinine: -0.198+/-0.086) in solute transport than pattern 1 patients (deltaD/P creatinine: -0.036+/-0.077, P<0.05). CONCLUSIONS These results suggest that a progressive decrease of the CD4/CD8 ratio in PDE correlates with a persistent expression of TGF-beta1, and plays a pathogenetic role in the evolution of peritonitis, PET deterioration and peritoneal fibrosis. Therefore, patterns of CD4/CD8 T-cell ratio in PDE may predict clinical outcomes of peritonitis in CAPD patients.
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Affiliation(s)
- Hsin-Hui Wang
- Department of Pediatrics, Section of Nephrology, Taipei Veterans General Hospital, and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
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Abstract
The incidence of peritonitis in peritoneal dialysis (PD) has further decreased after the introduction of automated peritoneal dialysis (APD) into clinical routine. Technical advances such as a reduction in the number of connections, more motivated patients, and improved host defense mechanisms in APD have been described. We found that the long daytime interval without dialysate exchanges leads to a higher absolute number of peritoneal macrophages which are capable of an improved first-line host defense. This is demonstrated by a higher release of cytokines of peritoneal macrophages after stimulation with lipopolysaccharides. The dry "day" in nightly intermittent PD seems to have no relevant additional positive effects on peritoneal host defense compared to continuous cyclic peritoneal dialysis. The regeneration of peritoneal cell populations induced by intervals without PD remains relevant even in times when more "biocompatible" PD solutions become available.
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CHOW KM, WONG WS, CHOW VCY, WONG TYH, CHAN NPH, LI PKT. Role of macrophages in tuberculous peritonitis: longitudinal follow-up of 16 continuous ambulatory peritoneal dialysis patients. ACTA ACUST UNITED AC 2002. [DOI: 10.1016/s1561-5413(09)60086-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
Considering experience acquired in the past years, it seems as though physicians have reached a plateau in the frequency of peritonitis. A peritonitis rate of 1 every 2 patient years may be acceptable. Further reduction of this peritonitis rate will require inordinately large efforts on all fronts. One will have to consider what are the acceptable costs and risks of peritonitis in patients on peritoneal dialysis. New developments in catheter technology, improved connections, better understanding of patient selection and training programs, improved diagnostic and therapeutic methods in the management of peritonitis, and understanding of the infectious and immune processes are eagerly awaited developments.
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Affiliation(s)
- S Vas
- Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Cohen ML, Douvdevani A, Chaimovitz C, Shany S. Regulation of TNF-alpha by 1alpha,25-dihydroxyvitamin D3 in human macrophages from CAPD patients. Kidney Int 2001; 59:69-75. [PMID: 11135059 DOI: 10.1046/j.1523-1755.2001.00467.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND We have previously reported that 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] accumulates in the dialysis fluid of uremic patients treated by continuous ambulatory peritoneal dialysis (CAPD). It has been reported that this metabolite regulates the production of cytokines by monocytes/macrophages. Since tumor necrosis factor-alpha (TNF-alpha) initiates an inflammatory cascade during peritonitis, the aim of the present study was to investigate the effect of 1alpha, 25(OH)2D3 on the production of TNF-alpha by human peritoneal macrophages (HPMs). METHODS HPMs were obtained from patients on CAPD. Cells were incubated with various concentrations of 1alpha, 25(OH)2D3, 1alpha,24(S) dihydroxyvitamin D2 [1alpha,24(S)(OH)2D2] or 25-hydroxyvitamin D3 (25-OH-D3) for 16 hours. This was followed by lipopolysaccharide (LPS; 1 microg/mL) incubation for 2.5 to 6 hours. TNF-alpha protein production was determined by enzyme-linked immunosorbent assay. TNF-alpha mRNA was assayed by the reverse transcriptase-polymerase chain reaction procedure, using internal synthetic mRNA standards for quantitative results. RESULTS Incubation of HPMs with 1alpha,25(OH)2D3 prior to stimulation with LPS dose dependently inhibited the expression of TNF-alpha on both mRNA and protein levels. Similar results were obtained with the less calcemic vitamin D2 analogue 1alpha,24(S)(OH)2D2. Incubation of HPMs with 25-OH-D3 also revealed a down-regulation of TNF-alpha expression. Since this down-regulatory effect was blocked by ketoconazole, it is likely that this effect was caused by the conversion of 25-OH-D3 into 1alpha,25(OH)2D3 by HPMs. CONCLUSIONS 1alpha,25(OH)2D3 has a potent inhibitory effect on the production of TNF-alpha by LPS-activated HPMs. We hypothesize that 1alpha, 25(OH)2D3 may constitute a regulatory mechanism that, by controlling the intensity of the inflammatory response of the peritoneum, will moderate tissue damage during peritonitis.
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Affiliation(s)
- M L Cohen
- Departments of Clinical Biochemistry and Nephrology, Faculty of Health Sciences, Ben-Gurion University of the Negev,Soroka Medical Center, Beer Sheva, Israel
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Abstract
The frequency, pathology, animal models, pathogenesis, clinical manifestations, diagnostic criteria, therapy and prevention of peritoneal sclerosis are reviewed. Many of these aspects have a bimodal configuration which suggests that peritoneal sclerosis, usually considered a single pathology in peritoneal dialysis, is actually two distinct nosological entities: simple sclerosis and sclerosing peritonitis. The former is very frequent, with minor anatomical alterations and low clinical impact; it is reproducible in animals by means of peritoneal dialysis, and is clearly due to the poor biocompatibility of peritoneal dialysis solutions. The latter is rare, with radical anatomical alterations and high mortality requiring valid methods of diagnosis, therapy and prevention; it can only be reproduced in animal models by means other than peritoneal dialysis and seems to be due to factors both related and unrelated to peritoneal dialysis.
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Affiliation(s)
- G Garosi
- Nephrology and Dialysis Department, Le Scotte Hospital, Siena, Italy.
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47
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Affiliation(s)
- R J Faull
- Renal Unit, Royal Adelaide Hospital, Australia.
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van Rossen ME, Stoop MP, Hofland LJ, van Koetsveld PM, Bonthuis F, Jeekel J, Marquet RL, van Eijck CH. Red blood cells inhibit tumour cell adhesion to the peritoneum. Br J Surg 1999; 86:509-13. [PMID: 10215826 DOI: 10.1046/j.1365-2168.1999.01050.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Perioperative blood transfusion has been associated with increased tumour recurrence and poor prognosis in colorectal cancer. Blood loss in the peritoneal cavity might be a tumour-promoting factor for local recurrence. The aim of this study was to investigate whether blood in the peritoneal cavity affects local tumour recurrence. METHODS In an established in vivo rat model the effect of 1.5 ml syngeneic whole blood on tumour cell adhesion and tumour growth was investigated. In the same model the effect of 1.5 ml pure red blood cell (RBC) concentrate and 1.5 ml RBC-derived substances on tumour cell adhesion was studied. In an established in vitro model the effect of increasing numbers of RBCs (0-250 bx 10(6)) on tumour cell adhesion and tumour growth was assessed. RESULTS Both the presence of blood and RBC concentrate in the peritoneal cavity prevented tumour cell adhesion in vivo (overall P </= 0.001 and P </= 0.05 respectively), rather than promoting adherence. RBC concentrate and RBC-derived substances had a comparable inhibitory effect on tumour cell adhesion. In in vitro studies RBCs inhibited tumour cell adhesion but not tumour growth. CONCLUSION RBC-derived factors prevent tumour cell adhesion to the peritoneum, and consequently tumour recurrence.
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Affiliation(s)
- M E van Rossen
- Laboratory for Experimental Surgery, Erasmus University Rotterdam, Rotterdam, The Netherlands
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Brauner A, Lu Y, Halldén G, Hylander B, Lundahl J. Difference in the blood monocyte phenotype between uremic patients and healthy controls: its relation to monocyte differentiation into macrophages in the peritoneal cavity. Inflammation 1998; 22:55-66. [PMID: 9484650 DOI: 10.1023/a:1022395723972] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The phenotypic alterations between blood monocytes from 11 patients with end-stage renal disease, who had been on peritoneal dialysis for less than one week, and blood monocytes from 10 healthy controls, were analyzed. In addition, peritoneal macrophages in the dialysate effluent were enclosed. Analysis of functional receptor density was performed using immunostaining and flow cytometry. The phenotypic characterization was selected to represent various biological functions such as adhesion, phagocytosis (CD11b/CD18, CD11c/CD18, CD16), antigen-presentation (HLA-DR, ICAM-1), differentiation (transferrin receptor, CD71), receptor for LPS (CD14) and initiation of the coagulation cascade (Tissue factor, CD142). The proportion of CD16-positive blood monocytes and the quantitative level of ICAM-1 were higher in the patient group, compared to healthy controls. A significant increase in the quantitative level of CD11b/CD18, CD11c/CD18, HLA-DR and ICAM-1, transferrin receptor, CD14 and CD16, was found on peritoneal macrophages, compared to monocytes, harvested both from the corresponding patients, as well as from healthy donors. In contrast, we did not find any significant differences in the expression of tissue factor between monocytes and peritoneal macrophages. In conclusion, phenotypic differences exist between monocyte populations in the blood circulation of CAPD patients, and healthy individuals. We also show that transmigration of monocytes into the peritoneal cavity implies a selective up-regulation of functional receptors, preferentially related to adhesion, and antigen-presentation in a steady-state situation in non-infected CAPD patients.
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Affiliation(s)
- A Brauner
- Dept of Microbiology, Karolinska Hospital Stockholm, Sweden
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Plum J, Schoenicke G, Grabensee B. Osmotic agents and buffers in peritoneal dialysis solution: monocyte cytokine release and in vitro cytotoxicity. Am J Kidney Dis 1997; 30:413-22. [PMID: 9292571 DOI: 10.1016/s0272-6386(97)90287-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Peritonitis remains a major problem in peritoneal dialysis. The incidence of peritonitis may be reduced by the use of more "biocompatible" peritoneal dialysis solutions that do not impair local host defense mechanisms, such as occurs with conventional lactate-buffered glucose solutions. In the present study, we investigated the use of bicarbonate and lactate as buffer systems and glucose, amino acids, and glucose polymer as osmotic agents on specific cellular functions of isolated fresh blood monocytes in vitro. The bicarbonate-buffered solutions had a physiologic pH (7.0 to 7.6). Lactate-buffered solutions were tested with a pH between 5.5 and 7.3. RPMI 1640 (Roswell Park Memorial Institute, supplied by Biochrom, Berlin, Germany) and phosphate-buffered saline were used as control mediums. The test solutions were incubated with 200,000 monocytes/mL for 45 minutes followed by a 1:1 mix with RPMI 1640 (with supplements) during a 24- or 4-hour tetrazolium bromide test (MTT test) recovery period. Constitutive and lipopolysaccharide (LPS)-stimulated release of interleukin-1beta (IL-1beta) and IL-6 in the supernatants as parameters of cellular host defense and lactate dehydrogenase concentrations and MTT-formazan production as parameters for cell cytotoxicity were measured. Significantly higher IL-6 and IL-1beta release was found in the bicarbonate-buffered solutions, both under basal conditions and after LPS stimulation, compared with the lactate-buffered solutions (LPS stimulation: 1% amino acids/34 mmol/L bicarbonate, IL-1beta: 1,166 +/- 192 pg/mL; 1.5% glucose/34 mmol/L bicarbonate, IL-1beta: 752 +/- 107 pg/mL; 1.5% glucose/35 mmol/L lactate/pH 5.5, IL-1beta: 174 +/- 51 pg/mL). Some of these differences could even be detected in spent dialysate after a 6-hour dwell in continuous ambulatory peritoneal dialysis patients (n = 10). A lower degree of cellular cytotoxicity (lactate dehydrogenase activity) and better-preserved metabolic activity (MTT test) also were found for the bicarbonate-buffered solutions. Amino acids (1%) proved to be comparable to glucose (1.5%) as an osmotic agent at a neutral pH with regard to LPS-stimulated cytokine release and cytotoxicity. The incubation with a glucose polymer solution (7.5% glucose polymer in phosphate-buffered saline, pH 7.3) resulted in a significantly lowered cytokine release (LPS stimulation: IL-1beta, 69 +/- 19 pg/mL) compared with the other solutions with neutral pH (P < 0.01). These results suggest that bicarbonate as a buffer provided better biocompatibility with regard to mononuclear cytokine release and viability compared with lactate. Amino acids and glucose were equivalent to these parameters at a physiologic pH. The glucose polymer solution, however, was associated with a marked depression of cytokine release.
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Affiliation(s)
- J Plum
- Department of Nephrology and Rheumatology, Heinrich-Heine University Dusseldorf, Germany
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