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Umemura K, Shimoda H, Ishido K, Kimura N, Wakiya T, Kagiya T, Sato K, Mitsuhashi Y, Watanabe S, Narita H, Chiba T, Hakamada K. Microanatomical organization of hepatic venous lymphatic system in humans. PLoS One 2023; 18:e0286316. [PMID: 37228087 DOI: 10.1371/journal.pone.0286316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 05/13/2023] [Indexed: 05/27/2023] Open
Abstract
Lymphatic fluid drains from the liver via the periportal lymphatic, hepatic venous lymphatic, and superficial lymphatic systems. We performed a postmortem study to clarify the three-dimensional structure and flow dynamics of the human hepatic venous lymphatic system, as it still remains unclear. Livers were excised whole from three human cadavers, injected with India ink, and sliced into 1-cm sections from which veins were harvested. The distribution of lymphatic vessels was observed in 5 μm sections immunostained for lymphatic and vascular markers (podoplanin and CD31, respectively) using light microscopy. Continuity and density of lymphatic vessel distribution were assessed in en-face whole-mount preparations of veins using stereomicroscopy. The structure of the external hepatic vein wall was assessed with scanning electron microscopy (SEM). The lymphatic dynamics study suggested that lymphatic fluid flows through an extravascular pathway around the central and sublobular veins. A lymphatic vessel network originates in the wall of sublobular veins, with a diameter greater than 110 μm, and the peripheral portions of hepatic veins and continues to the inferior vena cava. The density distribution of lymphatic vessels is smallest in the peripheral portion of the hepatic vein (0.03%) and increases to the proximal portion (0.22%, p = 0.012) and the main trunk (1.01%, p < 0.001), correlating positively with increasing hepatic vein diameter (Rs = 0.67, p < 0.001). We revealed the three-dimensional structure of the human hepatic venous lymphatic system. The results could improve the understanding of lymphatic physiology and liver pathology.
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Affiliation(s)
- Kotaro Umemura
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hiroshi Shimoda
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Neuroanatomy, Cell Biology, Histology, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Keinosuke Ishido
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Norihisa Kimura
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Takuji Kagiya
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Kentaro Sato
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Yuto Mitsuhashi
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Seiji Watanabe
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hirokazu Narita
- Biomedical Science and Engineering Research Center, Hakodate Medical Association Nursing and Rehabilitation Academy, Hakodate, Hokkaido, Japan
| | - Tomohiro Chiba
- Department of Anatomical Science, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Hirosaki, Aomori, Japan
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Yoshihara T, Okabe Y. Aldh1a2 + fibroblastic reticular cells regulate lymphocyte recruitment in omental milky spots. J Exp Med 2023; 220:213908. [PMID: 36880532 PMCID: PMC9997506 DOI: 10.1084/jem.20221813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 12/29/2022] [Accepted: 02/03/2023] [Indexed: 03/06/2023] Open
Abstract
Lymphoid clusters in visceral adipose tissue omentum, known as milky spots, play a central role in the immunological defense in the abdomen. Milky spots exhibit hybrid nature between secondary lymph organs and ectopic lymphoid tissues, yet their development and maturation mechanisms are poorly understood. Here, we identified a subset of fibroblastic reticular cells (FRCs) that are uniquely present in omental milky spots. These FRCs were characterized by the expression of retinoic acid-converting enzyme, Aldh1a2, and endothelial cell marker, Tie2, in addition to canonical FRC-associated genes. Diphtheria toxin-mediated ablation of Aldh1a2+ FRCs resulted in the alteration in milky spot structure with a significant reduction in size and cellularity. Mechanistically, Aldh1a2+ FRCs regulated the display of chemokine CXCL12 on high endothelial venules (HEVs), which recruit blood-borne lymphocytes from circulation. We further found that Aldh1a2+ FRCs are required for the maintenance of peritoneal lymphocyte composition. These results illustrate the homeostatic roles of FRCs in the formation of non-classical lymphoid tissues.
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Affiliation(s)
- Tomomi Yoshihara
- Laboratory of Immune Homeostasis, WPI Immunology Frontier Research Center, Osaka University , Osaka, Japan
| | - Yasutaka Okabe
- Laboratory of Immune Homeostasis, WPI Immunology Frontier Research Center, Osaka University , Osaka, Japan.,Center for Infectious Disease Education and Research, Osaka University , Osaka, Japan.,Japan Science and Technology Agency , PRESTO, Kawaguchi, Japan
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Gotloib L, Wajsbrot V, Shostak A. Osmotic Agents Hamper Mesothelial Repopulation as Seen in the Doughnut In Vivo Model. Perit Dial Int 2020. [DOI: 10.1177/089686080502503s07] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
♦ Background The problem of mesothelial cell injury derived from the use of peritoneal dialysis solutions has been explored deeply. Conversely, the eventual detrimental effects upon mesothelial cell regeneration have awaked less investigative efforts than those focused on injury. ♦ Objective To evaluate in the in vivo and in situ rat “doughnut” model of mesothelial repopulation, the eventual effect of peritoneal lavage with Hank's Balanced Salt Solution (HBSS) as well as that of 4.25% glucose and 7.5% icodextrin dialysis solutions. ♦ Experimental Animals 100 Sprague–Dawley albino rats were included in the study. Animals were divided into five groups of 20 rats each: group 1: control at zero time; group 2: sham-injected rats; group 3: rats exposed to HBSS; group 4: rats treated with 4.25% glucose peritoneal dialysis solution; group 5: rats injected with 7.5% icodextrin. ♦ Methods Selective exfoliation of a ring of mesothelium (width 0.8 mm, diameter 4 mm) covering the anterior surface of the liver was performed in 80 animals. The control zero-time group was used to evaluate the normal density distribution of the mesothelial cells forming the monolayer. The other groups were treated by means of daily sham injections or intraperitoneal infusion of each experimental solution for a period of 30 consecutive days. After a recovery period of 15 days, imprints and biopsies from the monolayer covering the exfoliated area were taken and processed for light microscopy. ♦ Results Macroscopic observation of the abdominal cavity at the end of the 15-day recovery period showed that the prevalence of fibrotic adhesions between the peritoneal exfoliated area and the neighboring diaphragm was 10% for the sham-injected group, 5% for the HBSS-exposed animals, 85% for the rats injected with 4.25% glucose, and 95% for the icodextrin-treated group. Prevalence of fibrous adhesions in sham-injected animals and rats exposed to HBSS were devoid of statistically significant differences. Conversely, comparison of these groups with results observed in animals treated with the osmotic agents was significant, at the p < 0.0039 level. Regarding density distribution of mesothelial cells observed in imprints, there were no significant differences between the control zero-time and the sham-injected group. This parameter was marginally lower ( p < 0.05) in the HBSS-treated rats. Imprints were not taken from animals exposed to glucose or icodextrin because a dense layer of connective tissue replaced the exfoliated mesothelial area. ♦ Conclusions Observations made in this study support the contention that both osmotic agents, 4.25% glucose and 7.5% icodextrin, substantially restrain the normal process of mesothelial cell repopulation and induce repair by means of connective tissue. The underlying mechanism is most likely sustained oxidative stress.
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Affiliation(s)
- Lazaro Gotloib
- Department of Nephrology & Hypertension and the Research Center for Experimental Nephrology, “Ha'Emek” Medical Center, Afula, Israel
| | - Valery Wajsbrot
- Department of Nephrology & Hypertension and the Research Center for Experimental Nephrology, “Ha'Emek” Medical Center, Afula, Israel
| | - Avshalom Shostak
- Department of Nephrology & Hypertension and the Research Center for Experimental Nephrology, “Ha'Emek” Medical Center, Afula, Israel
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Di Paolo N, Sacchi G, Garosi G, Sansoni E, Bargagli L, Ponzo P, Tanganelli P, Gaggiotti E. Omental Milky Spots and Peritoneal Dialysis — Review and Personal Experience. Perit Dial Int 2020. [DOI: 10.1177/089686080502500111] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Little research has been dedicated to milky spots (MS), except for their role in oncology. In the field of peritoneal dialysis (PD), studying MS could help in understanding peritoneal defenses. Methods We reviewed the methods for detecting and counting omental MS and studied modifications induced by chemical and inflammatory stimuli. The reactions of MS to peritoneal catheters, PD solutions, and infection were studied in 32 rabbits. We also evaluated changes in MS in 39 serial omental biopsies from 16 patients with different histories of PD, and examined peritoneal biopsies from 38 patients with sclerosing peritonitis. Results The catheter provoked an immediate increase in the number and size of MS in rabbits. Intraperitoneal infusion of commercial PD solution containing 1.38% or 3.86% glucose for 30 days led to a slight but significant increase in the number and size of MS, without differences between the two glucose concentrations. Peritonitis caused a sharp increase in the number of MS in rabbits and humans, and a particular transformation. In patients with simple sclerosis, we observed normal MS having the same number and size as in patients without simple sclerosis. A few MS were found in only 2 patients with sclerosing peritonitis. Conclusions Peritoneal dialysis activates omental MS. Peritoneal infection leads to a marked increase in the activity of MS, some of which undergo a singular transformation, casting doubt on previous theories about differentiation of MS from other lymphatic organs. Comparison with oncological studies indicates certain contact points. The presence of MS in PD patients with simple sclerosis is in contradiction to other morphological studies sustaining that MS act only when in contact with a fenestrated mesothelial basement membrane. Finally, the shortage of MS in patients with sclerosing peritonitis raises certain questions about etiopathogenesis.
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Affiliation(s)
- Nicola Di Paolo
- Nephrology and Dialysis Department, University of Siena, Italy
| | - Giovanni Sacchi
- Siena University Hospital; Institute of Neuroscience, University of Siena, Italy
| | - Guido Garosi
- Nephrology and Dialysis Department, University of Siena, Italy
| | - Enrico Sansoni
- Nephrology and Dialysis Department, University of Siena, Italy
| | - Lucia Bargagli
- Siena University Hospital; Institute of Neuroscience, University of Siena, Italy
| | - Paola Ponzo
- Siena University Hospital; Institute of Neuroscience, University of Siena, Italy
| | - Piero Tanganelli
- Human Pathology and Oncology Department, University of Siena, Italy
| | - Enzo Gaggiotti
- Nephrology and Dialysis Department, University of Siena, Italy
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Abstract
Accumulating evidence highlights the importance of interactions between tumour cells and stromal cells for tumour initiation, progression, and metastasis. In tumours that contain adipocyte in their stroma, adipocytes contribute to modification of tumour microenvironment and affect metabolism of tumour and tumour progression by production of cytokines and adipokines from the lipids. The omentum and bone marrow (BM) are highly adipocyte-rich and are also common metastatic and primary tumour developmental sites. Omental adipocytes exhibit metabolic cross-talk, immune modulation, and angiogenesis. BM adipocytes secrete adipokines, and participate in solid tumour metastasis through regulation of the CCL2/CCR2 axis and metabolic interactions. BM adipocytes also contribute to the progression of hematopoietic neoplasms. Here, we here provide an overview of research progress on the cross-talks between omental/BM adipocytes and tumour cells, which may be pivotal modulators of tumour biology, thus highlighting novel therapeutic targets. Abbreviations: MCP-1, monocyte chemoattractant protein 1IL, interleukinSTAT3, signal transducer and activator of transcription 3FABP4, fatty acid binding protein 4PI3K/AKT, phosphoinositide 3-kinase/protein kinase BPPAR, peroxisome proliferator-activated receptorPUFA, polyunsaturated fatty acidTAM, tumour-associated macrophagesVEGF, vascular endothelial growth factorVEGFR, vascular endothelial growth factor receptorBM, bone marrowBMA, bone marrow adipocytesrBMA, regulated BMAcBMA, constitutive BMAUCP-1, uncoupling protein-1TNF-α, tumour necrosis factor-alphaRANKL, receptor activator of nuclear factor kappa-Β ligandVCAM-1, vascular cell adhesion molecule 1JAK2, Janus kinase 2CXCL (C–X–C motif) ligandPGE2, prostaglandin E2COX-2, cyclooxygenase-2CCL2, C-C motif chemokine ligand 2NF-κB, nuclear factor-kappa BMM, multiple myelomaALL, acute lymphoblastic leukemiaAML, acute myeloid leukemiaGDF15, growth differentiation factor 15AMPK, AMP-activated protein kinaseMAPK, mitogen-activated protein kinaseAPL, acute promyelocytic leukemiaCCR2, C-C motif chemokine receptor 2SDF-1α, stromal cell-derived factor-1 alphaFFA, free fatty acidsLPrA, leptin peptide receptor antagonistMCD, malonyl-CoA decarboxylase.
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Affiliation(s)
- Yoon Jin Cha
- Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
| | - Ja Seung Koo
- Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
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Veenstra KA, Alnabulsi A, Tubbs L, Ben Arous J, Secombes CJ. Immunohistochemical examination of immune cells in adipose tissue of rainbow trout (Oncorhynchus mykiss) following intraperitoneal vaccination. FISH & SHELLFISH IMMUNOLOGY 2019; 87:559-564. [PMID: 30731214 DOI: 10.1016/j.fsi.2019.02.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 01/31/2019] [Accepted: 02/01/2019] [Indexed: 06/09/2023]
Abstract
Mammalian perivisceral adipose has been shown to play an important role in the regulation of the peritoneal immune responses. Recently it has been demonstrated that peritoneal antigens are collected by leukocytes within the visceral adipose mass, and a broad range of immunomodulatory genes are differentially expressed in adipose tissue after intraperitoneal vaccination in rainbow trout. To assess the immune cell component in adipose, immunohistochemical analysis was used to examine B-cell, T-cell and antigen presenting cell (APC) numbers and distribution in rainbow trout adipose tissue 24 and 72 h post vaccination in comparison to control fish. The results of this study support previous work on mammals with omental milky spots in naïve fish found to contain APCs and T-cells which then increased in size, number and complexity following vaccination. It suggests that following peritoneal stimulation the visceral adipose mass in fish likely plays an important role in vaccine antigen uptake and presentation by APCs, as well as subsequent T-cell activation and differentiation.
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Affiliation(s)
- Kimberly A Veenstra
- Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK.
| | - Ayham Alnabulsi
- Vertebrate Antibodies Ltd., Zoology Building, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK.
| | - Lincoln Tubbs
- Elanco Animal Health, Food Animal Vaccines R&D, 2500 Innovation Way, Greenfield, IN, 46140, USA.
| | - Juliette Ben Arous
- Seppic, 50 Boulevard National, La Garenne-Colombes, Paris, 92250, France.
| | - Christopher J Secombes
- Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, AB24 2TZ, UK.
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Huyghe S, de Rooster H, Doom M, Van den Broeck W. The Microscopic Structure of the Omentum in Healthy Dogs: The Mystery Unravelled. Anat Histol Embryol 2015. [PMID: 26201371 DOI: 10.1111/ahe.12189] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
The canine omentum has many valuable properties but is still an underestimated organ. It contributes in many ways to the protection of the peritoneal cavity through its versatility on immunological level, but also through its role during angiogenesis, absorption, adhesion and fat storage. Despite a wide range of applications, the basic structure of the omentum is not well documented. This study provides an insight in the microscopic structure of the canine omentum through both light microscopic and electron microscopic investigations. Two regions could be distinguished in the canine omentum: translucent and adipose-rich regions. The translucent regions were composed of two different layers: a continuous flattened mesothelium on top of a submesothelial connective tissue matrix. The adipose-rich regions consisted of a substantial layer of adipocytes on which a flattened continuous mesothelium was present. Between those two layers, a few strands of collagen fibres could be detected. Large aggregates of immune cells, the so-called milky spots, were not observed in the omentum of healthy dogs. Only a limited number of leucocytes, macrophages and neutrophils were found, scattered throughout the connective tissue in the translucent regions. At the level of the adipose-rich regions, the immunological population was virtually non-existent.
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Affiliation(s)
- S Huyghe
- Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium
| | - H de Rooster
- Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium
| | - M Doom
- Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium
| | - W Van den Broeck
- Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium
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Regulation of Phagocyte Migration by Signal Regulatory Protein-Alpha Signaling. PLoS One 2015; 10:e0127178. [PMID: 26057870 PMCID: PMC4461249 DOI: 10.1371/journal.pone.0127178] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 04/13/2015] [Indexed: 01/13/2023] Open
Abstract
Signaling through the inhibitory receptor signal regulatory protein-alpha (SIRPα) controls effector functions in phagocytes. However, there are also indications that interactions between SIRPα and its ligand CD47 are involved in phagocyte transendothelial migration. We have investigated the involvement of SIRPα signaling in phagocyte migration in vitro and in vivo using mice that lack the SIRPα cytoplasmic tail. During thioglycolate-induced peritonitis in SIRPα mutant mice, both neutrophil and macrophage influx were found to occur, but to be significantly delayed. SIRPα signaling appeared to be essential for an optimal transendothelial migration and chemotaxis, and for the amoeboid type of phagocyte migration in 3-dimensional environments. These findings demonstrate, for the first time, that SIRPα signaling can directly control phagocyte migration, and this may contribute to the impaired inflammatory phenotype that has been observed in the absence of SIRPα signaling.
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Characterization of mouse mediastinal fat-associated lymphoid clusters. Cell Tissue Res 2014; 357:731-41. [PMID: 24853670 DOI: 10.1007/s00441-014-1889-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 04/08/2014] [Indexed: 01/06/2023]
Abstract
The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs "mediastinal fat-associated lymphoid clusters". These clusters can be considered as niches for Th cell production.
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Milky spots promote ovarian cancer metastatic colonization of peritoneal adipose in experimental models. THE AMERICAN JOURNAL OF PATHOLOGY 2013; 183:576-91. [PMID: 23885715 DOI: 10.1016/j.ajpath.2013.04.023] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Revised: 03/19/2013] [Accepted: 04/16/2013] [Indexed: 12/17/2022]
Abstract
The goal of controlling ovarian cancer metastasis formation has elicited considerable interest in identifying the tissue microenvironments involved in cancer cell colonization of the omentum. Omental adipose is a site of prodigious metastasis in both ovarian cancer models and clinical disease. This tissue is unusual for its milky spots, comprised of immune cells, stromal cells, and structural elements surrounding glomerulus-like capillary beds. The present study shows the novel finding that milky spots and adipocytes play distinct and complementary roles in omental metastatic colonization. In vivo assays showed that ID8, CaOV3, HeyA8, and SKOV3ip.1 cancer cells preferentially lodge and grow within omental and splenoportal fat, which contain milky spots, rather than in peritoneal fat depots. Similarly, medium conditioned by milky spot-containing adipose tissue caused 75% more cell migration than did medium conditioned by milky spot-deficient adipose. Studies with immunodeficient mice showed that the mouse genetic background does not alter omental milky spot number and size, nor does it affect ovarian cancer colonization. Finally, consistent with the role of lipids as an energy source for cancer cell growth, in vivo time-course studies revealed an inverse relationship between metastatic burden and omental adipocyte content. Our findings support a two-step model in which both milky spots and adipose have specific roles in colonization of the omentum by ovarian cancer cells.
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Roman A, Kuśmierczyk J, Klimek E, Rogóż Z, Nalepa I. Effects of co-administration of fluoxetine and risperidone on properties of peritoneal and pleural macrophages in rats subjected to the forced swimming test. Pharmacol Rep 2013; 64:1368-80. [PMID: 23406747 DOI: 10.1016/s1734-1140(12)70934-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Revised: 07/27/2012] [Indexed: 01/29/2023]
Abstract
BACKGROUND Literature data show that administration of atypical antipsychotic drug, risperidone (RIS), enhances antidepressive action of fluoxetine (FLU). As antidepressive treatments also regulate immune functions, we examined whether combined administration of FLU and RIS to rats subsequently subjected to a forced swimming test (FST) modifies parameters of macrophage activity that are directly related to their immunomodulatory functions, i.e., arginase (ARG) activity and nitric oxide (NO) synthesis. METHODS Antidepressive action of the drugs was assessed with FST. Peritoneal and pleural cells were eluted and selected parameters of immunoreactivity were assessed colorimetrically. RESULTS We found that the concomitant administration of FLU (10 mg/kg) and RIS (0.1 mg/kg) produced antidepressive-like effects in the FST,whereas the drugs were ineffective if administered separately. Stress related to the FST affected immune cell redistribution and changed some of the metabolic and immunomodulatory properties of macrophages. FLU administered to rats at a suboptimal dose for antidepressive action potently influenced macrophage immunomodulatory properties and redirected their activity toward anti-inflammatory M2 functional phenotype, as manifested by changes in the ARG/NO ratio. These effects resulted from a direct cellular influence of the drug, as well as its action via neuroendocrine pathways, as evidenced in peritoneal and pleural cells. Addition of RIS did not augment immunomodulatory action of FLU, though the combination showed antidepressant-like activity in the FST. CONCLUSIONS Our results suggest that when the drugs were administered together, FLU was potent enough to redirect macrophages toward M2 activity. It is also postulated that drug-induced changes in the immune system are not so closely related to antidepressant-like effects or might be secondary to those produced in the neuroendocrine system.
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Affiliation(s)
- Adam Roman
- Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
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12
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Koyasu S, Moro K. Th2-type innate immune responses mediated by natural helper cells. Ann N Y Acad Sci 2013; 1283:43-9. [PMID: 23617587 DOI: 10.1111/nyas.12106] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Natural helper (NH) cells are a newly identified innate lymphocyte population that responds to a combination of interleukin (IL)-2 and either IL-25 or IL-33 to produce large amounts of T helper cell type 2 (Th2) cytokines. NH cells have been identified in fat-associated lymphoid clusters (FALCs), produce Th2 cytokines constitutively without any stimulation, and support the self-renewal of B1 cells and IgA production by B cells. Large amounts of IL-5 and IL-13 produced upon helminth infection or in response to IL-33 can induce eosinophilia and goblet cell hyperplasia in the lung and intestine; these cytokines, which activate NH cells, play important roles in antihelminth immunity and allergic diseases such as asthma.
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Affiliation(s)
- Shigeo Koyasu
- Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
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13
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Innate Th2-type immune responses and the natural helper cell, a newly identified lymphocyte population. Curr Opin Allergy Clin Immunol 2011; 11:109-14. [PMID: 21301328 DOI: 10.1097/aci.0b013e3283448808] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE OF REVIEW We discuss recent progress in the understanding of Th2 cytokines derived from innate cells involved in the pathophysiology of various allergic diseases. RECENT FINDINGS Recent studies have identified a previously unrecognized lymphocyte population capable of producing Th2 cytokines in response to IL-25 and/or IL-33 independently of T or B cells. SUMMARY Newly identified cells responsive to IL-25 and/or IL-33 include natural helper cells, MPP, nuocytes and innate helper type 2 cells. These cells produce large amounts of Th2 cytokines, most notably IL-5 and IL-13, leading to eosinophilia and goblet cell hyperplasia and are critical for antihelminth reactions. IL-5 and IL-13 also play a role in pathophysiology of allergic diseases such as asthma and allergic diarrhea. There are similarities and differences between these newly identified cell populations. MPP cells can potentially differentiate to other myeloid cells, making this cell type distinct from the others. Natural helper cells constitutively produce Th2 cytokines, support the self-renewal of B1 cells and enhance IgA production. Unlike other innate Th2 producers, natural helper cells are present in fat-associated lymphoid clusters and likely play additional roles in the regulation of homeostasis in adipose tissues.
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Abstract
The T helper type 2 (Th2) immune response, characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, is a critical immune response against helminths invading cutaneous or mucosal sites. It also plays a critical role in the pathophysiology of allergic diseases such as asthma and allergic diarrhoea. The Th2 cytokines are induced soon after helminth infection, even before a pathogen-specific adaptive immune response is established. Recent studies have shed light on such innate Th2 cytokine production by formerly uncharacterized innate immune cells such as natural helper cells capable of producing Th2 cytokines in response to IL-25 and IL-33 independently of adaptive immune responses. These cells produce large amounts of Th2 cytokines, most notably IL-5 and IL-13, leading to eosinophilia and goblet cell hyperplasia. We discuss here the mechanisms of innate production of Th2 cytokines in host immune responses against helminth infection as well as allergic immune responses and the similarities and differences between recently identified Th2-cytokine producing cells.
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Affiliation(s)
- Shigeo Koyasu
- Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
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Wang ZB, Li M, Li JC. Recent advances in the research of lymphatic stomata. Anat Rec (Hoboken) 2010; 293:754-61. [PMID: 20186966 DOI: 10.1002/ar.21101] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Lymphatic stomata are small openings of lymphatic capillaries on the free surface of the mesothelium. The peritoneal cavity, pleural cavity, and pericardial cavity are connected with lymphatic system via these small openings, which have the function of active absorption. The ultrastructure of the lymphatic stomata and their absorption from the body cavities are important clinically, such as ascites elimination, neoplasm metastasis, and inflammatory reaction. The lymphatic stomata play an important role in the physiological and pathological conditions. Our previous study indicated for the first time that nitric oxide (NO) could regulate the opening and absorption of the lymphatic stomata. It could decrease the level of free intracellular calcium [Ca(2+)] through increasing the cyclic guanosine monophosphate (cGMP) level in the rat peritoneal mesothelial cells, thus regulating the lymphatic stomata. This process is related with the NO-cGMP-[Ca(2+)] signal pathway. In this review, we summarize the recent advances in understanding the development and the function of the lymphatic stomata. The ultrastructure and regulations of the lymphatic stomata are also discussed in this review.
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Affiliation(s)
- Zi-Bin Wang
- Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
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Saqib NU, McGuire PG, Howdieshell TR. The omentum is a site of stromal cell-derived factor 1alpha production and reservoir for CXC chemokine receptor 4-positive cell recruitment. Am J Surg 2010; 200:276-82. [PMID: 20591406 DOI: 10.1016/j.amjsurg.2009.08.031] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2009] [Revised: 08/31/2009] [Accepted: 08/31/2009] [Indexed: 11/26/2022]
Abstract
BACKGROUND The mechanism of the omental response to injury remains poorly defined. This study investigates the omental reaction to a foreign body, examining the role of a chemokine ligand/receptor pair known to play a crucial role in angiogenesis and wound healing. METHODS A ventral hernia, surgically created in the abdominal wall of 6 swine, was repaired with silicone sheeting to activate the omentum. Omental thickness was determined by ultrasonography. Serial stromal cell-derived factor 1alpha (SDF-1alpha) concentrations were measured in blood, wound, and peritoneal fluids by enzyme-linked immunosorbent assay. RESULTS During the 14-day study period, serial ultrasonography showed a 20-fold increase in omental thickness, and enzyme-linked immunosorbent assay revealed a 4-fold increase in SDF-1alpha concentration in local wound fluid. Omental vessel count and vascular surface area were 8- to 10-fold higher in reactive omentum. Immunohistochemistry showed nearly complete replacement of control omental fat with CXC chemokine receptor 4 (CXCR4)-positive cells by day 14. CONCLUSIONS Activated omentum, important in the SDF-1alpha/CXCR4 axis, may serve as an intraperitoneal reservoir for recruitment of circulating bone marrow-derived cells vital to healing.
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Affiliation(s)
- Naveed U Saqib
- Department of Surgery, University of New Mexico HSC, Albuquerque, 87131, USA
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Disrupting ovarian cancer metastatic colonization: insights from metastasis suppressor studies. JOURNAL OF ONCOLOGY 2010; 2010:286925. [PMID: 20300552 PMCID: PMC2838371 DOI: 10.1155/2010/286925] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2009] [Accepted: 12/06/2009] [Indexed: 01/12/2023]
Abstract
Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.
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Koyasu S, Moro K, Tanabe M, Takeuchi T. Natural helper cells: a new player in the innate immune response against helminth infection. Adv Immunol 2010; 108:21-44. [PMID: 21056728 DOI: 10.1016/b978-0-12-380995-7.00002-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The Th2-type immune response, characterized by the production of IL-4, IL-5, and IL-13, is a critical immune response against helminths invading cutaneous or mucosal sites. Th2 cytokines are induced soon after helminth infection, even before a pathogen-specific adaptive immune response is established. Although the expulsion and clearance of helminths usually requires pathogen-specific Th2-mediated immunity, early induction of Th2 cytokines during the innate immune phase is important for host protection from helminth invasion. Recent studies have shed light on such Th2 cytokine production by formerly uncharacterized innate immune cells such as a newly identified natural helper cell. We discuss here the mechanisms of innate production of Th2 cytokines in host immune responses against helminth infection.
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Affiliation(s)
- Shigeo Koyasu
- Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
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Carlow DA, Gold MR, Ziltener HJ. Lymphocytes in the Peritoneum Home to the Omentum and Are Activated by Resident Dendritic Cells. THE JOURNAL OF IMMUNOLOGY 2009; 183:1155-65. [DOI: 10.4049/jimmunol.0900409] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Kim MS, Sung BK, Ogay V, Choi CJ, Kim MS, Kang DI, Soh KS. Novel circulatory connection from the acupoint Zhong Wan(CV12) to pancreas. J Pharmacopuncture 2008. [DOI: 10.3831/kpi.2008.11.1.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Sacchi G, Di Paolo N, Venezia F, Rossi A, Nicolai GA, Garosi G. Possible role of milky spots in mesothelial transplantation. Int J Artif Organs 2007; 30:520-6. [PMID: 17628853 DOI: 10.1177/039139880703000610] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Milky spots are very small omental organs, in contact with peritoneal membrane, devoid of capsule and consisting of macrophages, lymphocytes and a few plasma cells supported by blood and lymphatic vessels. The exact role of these particular organs is still not clear, but they are similar to lymphatic structures and it is clear that they play a role in peritoneal infection and abdominal tumors. Peritoneal dialysis seems to activate the milky spots changing their morphology. The authors try to formulate some hypotheses on the role played by these little omental organs during autologous mesothelial transplant.
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Affiliation(s)
- G Sacchi
- Department of Neuroscience, University of Siena, Siena, Italy
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Azadniv M, Dugger K, Bowers WJ, Weaver C, Crispe IN. Imaging CD8+ T cell dynamics in vivo using a transgenic luciferase reporter. Int Immunol 2007; 19:1165-73. [PMID: 17698980 DOI: 10.1093/intimm/dxm086] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
After activation, populations of antigen-specific T cells flow between sites of antigen expression, local lymphoid structures and other lymphoid and non-lymphoid organs. In this study, we documented the in vivo dynamics of a CD8(+) T cell response to antigen delivered using herpes simplex virus amplicon vectors and revealed several unexpected features. First, the T cells localized to the site of vector injection, as well as the draining lymph node within 24-48 h. Second, the major site to which T cells later redistributed were intra-abdominal lymphoid organs, including milky spots, mesenteric and lumbar lymph nodes. We determined the relationship between bioluminescent signal and antigen-specific T cell numbers in various lymphoid organs, and concluded that bioluminescent signal is a valid surrogate measure of T cell abundance in superficial lymph nodes, but not in deeper structures such as the spleen.
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Affiliation(s)
- Mitra Azadniv
- David H Smith Center for Microbiology and Immunology, Aab Institute for Biomedical Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
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Maroof A, English NR, Bedford PA, Gabrilovich DI, Knight SC. Developing dendritic cells become 'lacy' cells packed with fat and glycogen. Immunology 2005; 115:473-83. [PMID: 16011516 PMCID: PMC1782181 DOI: 10.1111/j.1365-2567.2005.02181.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
On maturation, dendritic cells (DCs) become highly active cells equipped for antigen uptake, migration and clustering and activation of T cells. We therefore asked whether DCs acquire fat and glycogen stores as they mature. DCs were generated from mouse bone marrow stem cells by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 7-8 days. Stimulation of the DCs with lipopolysaccharide (LPS) for the last 24 hr of culture, or exposure to 1-15 ng/ml of interleukin (IL)-4 during development, resulted in production of DCs not only with an increased ability to stimulate T cells but also with an increasingly lacy appearance on transmission electron microscopy, with multiple unstained areas in the cytoplasm. This changed morphology was associated with the presence of increasing amounts of fat and glycogen, identified by Sudan Black and periodic acid leukofushin/Schiff (PAS) staining, respectively. Lacy DCs up-regulated type 1 and type 2 scavenger receptors, providing possible mechanisms contributing to these changes. Lacy DCs were found occasionally amongst freshly isolated splenic and lymph node DCs. DCs can be isolated from human adipose tissue, and we tested whether lacy DCs acquiring fat and glycogen were present in mouse omentum. CD45+ cells migrating from the omentum expressed specific DC markers CD11c and 33D1, costimulatory molecules and major histocompatibility complex (MHC) class II, and most showed darkly staining fat inclusions. Thus, during development, DCs can acquire large amounts of fat and glycogen, accumulation of which is promoted by antigen exposure and modulated by the cytokine milieu and location, and which may act as a link between energy stores and immune function.
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Affiliation(s)
- Asher Maroof
- Antigen Presentation Research Group, Imperial College London, Harrow, UK
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Myers R, Greiner S, Harvey M, Soeffker D, Frenzke M, Abraham K, Shaw A, Rozenblatt S, Federspiel MJ, Russell SJ, Peng KW. Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer. Cancer Gene Ther 2005; 12:593-9. [PMID: 15746945 DOI: 10.1038/sj.cgt.7700823] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Oncolytic viruses are promising cytoreductive agents for cancer treatment but extensive human testing will be required before they are made commercially available. Here, we investigated the oncolytic potential of two commercially available live attenuated vaccines, Moraten measles and Jeryl-Lynn mumps, in a murine model of intraperitoneal human ovarian cancer and compared their efficacies against a recombinant oncolytic measles virus (MV-CEA) that is being tested in a phase I clinical trial. The common feature of these viruses is that they express hemagglutinin and fusion therapeutic proteins that can induce extensive fusion of the infected cell with its neighbors, resulting in death of the cell monolayer. In vitro, the three viruses caused intercellular fusion in human ovarian cancer cells but with marked differences in fusion kinetics. MV-CEA was the fastest followed by Jeryl-Lynn mumps virus while Moraten measles virus was the slowest, although all viruses eventually caused comparable cell death 6 days postinfection. Tumor-bearing mice treated with 10(6) or 10(7) pfu (one thousand times the vaccine dose) of each of the three viruses responded favorably to therapy with significant prolongations in survival. All three viruses demonstrated equivalent antitumor potency. Commercially available Moraten measles and Jeryl-Lynn mumps vaccines warrant further investigation as potential anticancer agents.
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Affiliation(s)
- Rae Myers
- Toxicology Core, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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Wilkosz S, Ireland G, Khwaja N, Walker M, Butt R, de Giorgio-Miller A, Herrick SE. A comparative study of the structure of human and murine greater omentum. ACTA ACUST UNITED AC 2005; 209:251-61. [PMID: 15662530 DOI: 10.1007/s00429-004-0446-6] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2004] [Indexed: 01/15/2023]
Abstract
In humans, the greater omentum is a fatty peritoneal fold that extends from the greater curvature of the stomach to cover most abdominal organs. It performs many functions, which include acting as a reservoir of resident peritoneal inflammatory cells, a storage site for lipid, and a regulator of fluid exchange in and out of the peritoneal cavity. Most importantly, the omentum readily adheres to areas of inflammation and peritoneal damage, often leading to adhesion formation. Despite its clinical importance, the omentum remains an understudied organ, and discrepancies exist as to its exact morphology. This study uses a combination of phase contrast microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) to elucidate the structure of the greater omentum of both human and mouse and determine whether it possesses a typical surface mesothelial cell lining similar to other serosa. Results indicated that both human and murine omenta were of similar structure and composed of two distinct types of tissue, one adipose-rich and the other translucent and membranous. The adipose-rich regions were well-vascularised and covered by a continuous mesothelial cell layer except at the sites of milky spots. In contrast, translucent areas were poorly vascularised and contained numerous fenestrations of varying size. The possible function and developmental origin of these gaps is unclear; however, their role in promoting omental adhesion formation and in the successful use of omental graft material is discussed.
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Affiliation(s)
- Sylwia Wilkosz
- Faculty of Life Sciences, University of Manchester, Room 3.239, Stopford Building, Oxford Road, M13 9PT, Manchester, UK
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Peng KW, Frenzke M, Myers R, Soeffker D, Harvey M, Greiner S, Galanis E, Cattaneo R, Federspiel MJ, Russell SJ. Biodistribution of oncolytic measles virus after intraperitoneal administration into Ifnar-CD46Ge transgenic mice. Hum Gene Ther 2004; 14:1565-77. [PMID: 14577918 DOI: 10.1089/104303403322495070] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
In support of a proposed phase I clinical trial, we studied the biodistribution of virus-infected cells after intraperitoneal administration of oncolytic measles viruses to alpha/beta interferon-defective mice expressing human CD46 with human-like tissue specificity. Various marker genes were employed, and green fluorescent protein proved to be most informative. Mesothelium and ovarian surface epithelium were remarkably resistant to infection, but infected peritoneal macrophages were present in abundance both in peritoneal lavage fluid and in the greater omentum, where they were heavily concentrated in "milky spots". Infected macrophages were also identified outside the peritoneal cavity, along the peritoneal fluid drainage pathway and in the spleen. Thus, diaphragmatic stomata, thoracic lymphatic vessels, and parathymic lymph nodes contained numerous measles-infected cells, as did the marginal zones of the white pulp of the spleen. Splenic marginal zone macrophages were the predominant targets of infection after intravenous administration of oncolytic measles viruses. When measles-infected peritoneal macrophages were adoptively transferred, they did not migrate beyond the confines of the peritoneal cavity, suggesting that, after intraperitoneal virus administration, the positive cells in thoracic lymphatics, parathymic lymph nodes, and spleen are nonmigratory cells transduced in situ by viral particles that have exited from the peritoneal cavity.
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Affiliation(s)
- Kah-Whye Peng
- Molecular Medicine Program, Guggenheim 18, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
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References. Perit Dial Int 2000. [DOI: 10.1177/089686080002003s08] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Abstract
The peritoneum is more than a mechanical covering that allows for the easy gliding of opposed peritoneal surfaces. The peritoneal mesothelial cells facilitate the action of powerful innate immune mechanisms. In addition, the peritoneal-associated lymphoid tissues contain unique cells that may play a crucial role in the localization of intraperitoneal infection. A clearer understanding of the molecular and cellular events underlying peritoneal functions in both the unstimulated and stimulated state will aid future treatment of peritonitis.
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Affiliation(s)
- J C Hall
- University Department of Surgery, Royal Perth Hospital, Australia
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Müller J, Yoshida T. Macrophage-colony forming cells (M-CFC), with different sensitivities to colony stimulating factors, from peritoneal exudates and tissues of chronically inflamed mice. Inflamm Res 1996; 45:593-9. [PMID: 8988404 DOI: 10.1007/bf02312041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVE AND DESIGN To determine whether nonadherent macrophage precursors are present within the inflamed peritoneal cavity in mice, we analysed the mononuclear cell populations from different peritoneal tissues. OBJECTS A group of 90 female mice BDF1 (C57BL/ 6 x DBA/2) was used for the study. Mononuclear cells were harvested from the peripheral blood, bone marrow, peritoneal exudate, omentum, mesentery, parietal peritoneum and diaphragm. TREATMENT Mice were injected intraperitoneally with 0.2 ml of Freund's incomplete adjuvant. Animals were sacrificed at 6, 13, 16, 21 and 30 days. Three to six animals were examined for each time period. METHODS Progenitor cell assay was performed in 1 ml of semi-solid agarose (0.3% Seakem GTG) DMEM which was supplied either with recombinant colony stimulating factors or with mesothelial cell-conditioned medium. RESULTS Nonadherent macrophage-colony forming cells were present in all peritoneal compartments (35-140 precursor cells/5 x 10(4) mononuclear cells). Granulocyte/ macrophage-colony forming cells were found in the inflamed omentum. Combined simultaneous treatment with GM-CSF and M-CSF blocked the proliferation of the exudate and mesentery-derived macrophage precursors, but not other peritoneal tissue-derived macrophage precursors. Sequential stimulation with GM-CSF and M-CSF did not inhibit macrophage colony formation. CONCLUSIONS GM-CSF can possibly influence the proliferative response induced by M-CSF. Nonadherent macrophage precursors recovered from different tissue compartments seem to differ in their sensitivity to growth regulation.
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Affiliation(s)
- J Müller
- Laboratory of Cell Pathology, Institute of Experimental Medicine, Praha, Czech Republic
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Abstract
The peritoneum is mainly protected by the innate immune system. This consists of mechanical clearance of the peritoneal cavity, activation of complement, and the actions of polymorphonuclear neutrophils and macrophages. The specific immune system, which is mediated by the activity of lymphocytes, provides a secondary amplification system that may be of great importance for patients with intraperitoneal sepsis. This review provides an overview of the relevant innate immune mechanisms and explores the possible role of peritoneum-associated lymphoid tissue.
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Affiliation(s)
- K A Heel
- University Department of Surgery, Royal Perth Hospital, Western Australia
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Shimotsuma M, Shirasu M, Hagiwara A, Takahashi T. Role of omentum-associated lymphoid tissue in the progression of peritoneal carcinomatosis. Cancer Treat Res 1996; 82:147-54. [PMID: 8849948 DOI: 10.1007/978-1-4613-1247-5_9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- M Shimotsuma
- First Department of Surgery, Kyoto Prefectural University of Medicine, Japan
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Doherty NS, Griffiths RJ, Hakkinen JP, Scampoli DN, Milici AJ. Post-capillary venules in the "milky spots" of the greater omentum are the major site of plasma protein and leukocyte extravasation in rodent models of peritonitis. Inflamm Res 1995; 44:169-77. [PMID: 7545527 DOI: 10.1007/bf01782815] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Intraperitoneal injection of inflammatory agents in the mouse and rat causes plasma protein and leukocyte extravasation into the peritoneal cavity. Following an intraperitoneal injection of zymosan A, the milky spots of the omentum were the only abdominal sites detected where intravenously administered Monastral Blue labeled interendothelial cell gaps responsible for plasma extravasation. In addition, when colored microspheres were intraventricularly administered to quantify blood flow, the omentum was the only abdominal organ which showed an increase in blood flow during zymosan A peritonitis. A combination of light and electron microscopy, plus measurement of myeloperoxidase activity (a marker of neutrophil accumulation) demonstrated that the omental milky spots are the major route through which leukocytes migrate into the peritoneal cavity. Identical structures in the pleura likewise are the sites of protein leakage into the pleural cavity. In contrast, selective sites of protein and cellular extravasation could not be detected in the synovial lining of the inflamed knee joint.
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Affiliation(s)
- N S Doherty
- Central Research Division, Pfizer Inc., Groton, CT 06340, USA
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