|
1
|
A novel activity on thymocytes cells exerted by the rattlesnake (Crotalus durissus cumanensis) venom. ACTA ACUST UNITED AC 2021; 41:449-457. [PMID: 34559492 PMCID: PMC8519596 DOI: 10.7705/biomedica.5599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Indexed: 11/30/2022]
Abstract
Introduction: The thymus is active mainly during the neonatal and pre-adolescent periods. Objective: To test naïve thymocytes proliferation and monocytes stimulation. Materials and methods: We collected fresh thymus tissue from neonate mice after surgery. Suspension cells were coated onto Ficoll-Hypaque support. The obtained cells (thymocytes) were cultured measuring the proliferation of naïve T cells stimulated by Crotalus durissus cumanensis (Cdc) venom at sub-lethal doses (20 ng). Then, we supplemented the wells with AlamarBlue™ and incubated them for 5 h to test their proliferation. Mononuclear cells from mice peripheral blood were collected and layered onto the support of the Ficoll-Hypaque solution. We added the thymocytes actively dividing (25 x 105 cells) from cultures stimulated with Cdc venom at 20 ng/well to cultured monocytes freshly obtained from the Ficoll-Hypaque separation. Both cell populations were incubated for 36 h until monocytes matured to macrophages. Results: The naïve thymocytes rapidly proliferated after stimulation with the Cdc venom (NTCdc) and these successively induced the maturation and function of monocytes progenitor cells to mature macrophages, which ingested Chinese ink. Conclusions: The naïve thymocytes proliferated by stimulation with the Cdc venom and subsequently the NT/Cdc induced the rapid maturation and function of monocytes progenitor cells becoming mature macrophages with their phenotypic characteristics.
Collapse
|
|
2
|
Melgar-Lesmes P, Luquero A, Parra-Robert M, Mora A, Ribera J, Edelman ER, Jiménez W. Graphene-Dendrimer Nanostars for Targeted Macrophage Overexpression of Metalloproteinase 9 and Hepatic Fibrosis Precision Therapy. NANO LETTERS 2018; 18:5839-5845. [PMID: 30096241 PMCID: PMC6377857 DOI: 10.1021/acs.nanolett.8b02498] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Fibrosis contributes to ∼45% of all deaths in industrialized nations, but no direct antifibrotic therapeutic interventions exist to date. Graphene-based nanomaterials exhibit excellent versatility in electronics, and emerging trends exploit their properties for biomedical applications, especially for drug and gene delivery. We designed constructs of graphene nanostars linked to PAMAM-G5 dendrimer for the selective targeting and delivery of a plasmid expressing the collagenase metalloproteinase 9 under the CD11b promoter into inflammatory macrophages in cirrhotic livers. Graphene nanostars preferentially accumulated in inflammatory macrophages M1 in less than 3 h in a manner unaffected by covalent linkage to dendrimers. Dendrimer-graphene nanostars efficiently delivered the plasmid encoding for metalloproteinase 9 into macrophages, allowing the synthesis and secretion of the metalloproteinase to digest adjacent collagen fibers. In turn, metalloproteinase 9 overexpression promoted the macrophage switch from inflammatory M1 to pro-regenerative M2 in 3 days. This targeted gene therapy reduced selectively and locally the presence of collagen fibers in fibrotic tracts where inflammatory macrophages accumulated in cirrhotic mice without affecting the activation state of hepatic stellate cells. Overall, this treatment significantly reduced hepatic injury and improved liver restoration in mice with liver cirrhosis treated for 10 days. Graphene-dendrimer nanostars targeted the macrophage overexpression of metalloproteinase 9, selectively reducing hepatic fibrosis, and might be a good treatment for diseases associated with fibrosis and inflammatory macrophage accumulation.
Collapse
Affiliation(s)
- Pedro Melgar-Lesmes
- Massachusetts Institute of Technology, Institute for Medical Engineering and Science, 77 Massachusetts Ave, Cambridge, MA 02139, USA
- Department of Biomedicine, School of Medicine, University of Barcelona, 143 Casanova, 08036 Barcelona, Spain
- Fundació Clínic per a la Recerca Biomèdica, Hospital Clínic Universitari, IDIBAPS, 149 Rosselló, 08036 Barcelona, Spain
| | - Aureli Luquero
- Department of Biomedicine, School of Medicine, University of Barcelona, 143 Casanova, 08036 Barcelona, Spain
| | - Marina Parra-Robert
- Biochemistry and Molecular Genetics Service, Hospital Clínic Universitari, IDIBAPS, CIBERehd, 170 Villarroel, 08036 Barcelona, Spain
| | - Adriana Mora
- Department of Biomedicine, School of Medicine, University of Barcelona, 143 Casanova, 08036 Barcelona, Spain
| | - Jordi Ribera
- Biochemistry and Molecular Genetics Service, Hospital Clínic Universitari, IDIBAPS, CIBERehd, 170 Villarroel, 08036 Barcelona, Spain
| | - Elazer R. Edelman
- Massachusetts Institute of Technology, Institute for Medical Engineering and Science, 77 Massachusetts Ave, Cambridge, MA 02139, USA
- Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
| | - Wladimiro Jiménez
- Department of Biomedicine, School of Medicine, University of Barcelona, 143 Casanova, 08036 Barcelona, Spain
- Biochemistry and Molecular Genetics Service, Hospital Clínic Universitari, IDIBAPS, CIBERehd, 170 Villarroel, 08036 Barcelona, Spain
| |
Collapse
|
|
3
|
Matos Filho ASDE, Petroianu A, Cardoso VN, Vidigal PVT. Splenic implant preservation after conservation in lactated Ringer´s solution. Rev Col Bras Cir 2018; 45:e1346. [PMID: 29451641 DOI: 10.1590/0100-6991e-20181346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 09/17/2017] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE to evaluate the morphology and function of autogenous splenic tissue implanted in the greater omentum, 24 hours after storage in Ringer-lactate solution. METHODS we divided 35 male rats into seven groups (n=5): Group 1: no splenectomy; Group 2: total splenectomy without implant; Group 3: total splenectomy and immediate autogenous implant; Group 4: total splenectomy, preservation of the spleen in Ringer-lactate at room temperature, then sliced and implanted; Group 5: total splenectomy, spleen sliced and preserved in Ringer-lactate at room temperature before implantation; Group 6: total splenectomy with preservation of the spleen in Ringer-lactate at 4°C and then sliced and implanted; Group 7: total splenectomy and the spleen sliced for preservation in Ringer-lactate at 4°C before implantation. After 90 days, we performed scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant and clot), haematological exams (erythrogram, leucometry, platelets), biochemical dosages (protein electrophoresis) and anatomopathological studies. RESULTS regeneration of autogenous splenic implants occurred in the animals of the groups with preservation of the spleen at 4ºC. The uptake of colloidal tin was higher in groups 1, 3, 6 and 7 compared with the others. There was no difference in hematimetric values in the seven groups. Protein electrophoresis showed a decrease in the gamma fraction in the group of splenectomized animals in relation to the operated groups. CONCLUSION the splenic tissue preserved in Ringer-lactate solution at 4ºC maintains its morphological structure and allows functional recovery after being implanted on the greater omentum.
Collapse
Affiliation(s)
| | - Andy Petroianu
- Department of Surgery, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | - Valbert Nascimento Cardoso
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, UFMG, Belo Horizonte, MG, Brazil
| | | |
Collapse
|
|
4
|
Spleen function after preservation in a physiological solution. J Surg Res 2015; 199:586-91. [PMID: 26119270 DOI: 10.1016/j.jss.2015.05.058] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 05/26/2015] [Accepted: 05/29/2015] [Indexed: 11/23/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the morphology and function of implanted autogenous spleen tissue after 24 h of preservation in a physiological solution. MATERIAL AND METHODS Thirty-five male rats were divided into seven groups (n = 5): group 1, without surgical procedure; group 2, total splenectomy; group 3, total splenectomy and immediate implant of autogenous spleen tissue; group 4, total splenectomy and preservation of the entire spleen in lactated Ringer solution at room temperature for 24 h, followed by spleen sectioning and implantation; group 5, total splenectomy, followed by spleen sectioning and preservation in lactated Ringer solution at room temperature for 24 h and subsequent implantation of the slices; group 6, total splenectomy and preservation of the entire spleen in lactated Ringer solution at 4°C for 24 h, followed by spleen sectioning and implantation; and group 7, total splenectomy, the spleen was sliced and preserved in lactate Ringer solution at 4°C for 24 h, followed by implantation of the slices. After 90 d, scintigraphic studies using sulfur colloid labeled with 99mTc of the liver, lungs, spleen, implants, and a blood clot were performed. Hematological (erythrogram, leukogram, and platelets) and histologic studies were carried out. RESULTS The autogenous splenic implants regenerated in all animals that received those implants preserved at 4°C and immediately after excision. The scintigraphic study showed a better phagocytic function in groups 1, 3, 6, and 7. No difference was observed in the hematological study. CONCLUSIONS Spleen tissue preserved in lactated Ringer solution at 4°C for 24 h maintains its vitality and capacity to recover hematological and phagocytic functions.
Collapse
|
|
5
|
Chen SY, Yang X, Feng WL, Liao JF, Wang LN, Feng L, Lin YM, Ren Q, Zheng GG. Organ-specific microenvironment modifies diverse functional and phenotypic characteristics of leukemia-associated macrophages in mouse T cell acute lymphoblastic leukemia. THE JOURNAL OF IMMUNOLOGY 2015; 194:2919-29. [PMID: 25662994 DOI: 10.4049/jimmunol.1400451] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Tumor-associated macrophages are widely studied in solid tumors. The distribution of macrophages in lymph node samples was found to be associated with the prognosis of lymphoma patients. However, the role of macrophages in leukemia and their functional and phenotypic characteristics in hematopoietic malignancies have not been defined. In this study, we examined the distribution and functional and phenotypic characteristics of macrophages in a Notch1-induced mouse model of T cell acute lymphoblastic leukemia (T-ALL). The distribution of macrophages in bone marrow (BM) and spleen, which are proposed as BM and spleen leukemia-associated macrophages (LAMs), were different during the development of leukemia. LAMs stimulated the proliferation of T-ALL cells and had higher migration activity. RNA-sequencing analysis revealed that gene expression profiles of BM and spleen LAMs showed considerable differences. RT-PCR analysis showed that LAMs expressed both M1- and M2-associated phenotypic genes, but they expressed much lower levels of TGF-β1, VEGF-A, and CSF-1 than did tumor-associated macrophages from B16 melanoma. Furthermore, spleen LAMs more potently stimulated the proliferation of T-ALL cells compared with BM LAMs. Moreover, LAMs could be subdivided into M1-like (CD206(-)) and M2-like (CD206(+)) groups. Both CD206(+) and CD206(-) LAMs stimulated the proliferation of T-ALL cells, although CD206(+) LAMs expressed higher levels of most M1- and M2-associated genes. These results suggested the functional and phenotypic characteristics of LAMs, which were modified by organ specific microenvironments. Our results broaden our knowledge about macrophages in malignant microenvironments from solid tumors to leukemia.
Collapse
Affiliation(s)
- Sha-Yan Chen
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Xiao Yang
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Wen-Li Feng
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Jin-Feng Liao
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Li-Na Wang
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Li Feng
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Yong-Min Lin
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Qian Ren
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and
| | - Guo-Guang Zheng
- State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
| |
Collapse
|
|
6
|
LU JING, BAI RUIHUA, QIN ZHENZHU, ZHANG YANYAN, ZHANG XIAOYAN, JIANG YANAN, YANG HONGYAN, HUANG YOUTIAN, LI GANG, ZHAO MINGYAO, DONG ZIMING. Differentiation of immature DCs into endothelial-like cells in human esophageal carcinoma tissue homogenates. Oncol Rep 2013; 30:739-44. [DOI: 10.3892/or.2013.2491] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Accepted: 05/02/2013] [Indexed: 11/06/2022] Open
|
|
7
|
Marques RG, Caetano CER, Diestel CF, Lima E, Portela MC, Oliveira AV, Oliveira MBN, Bernardo-Filho M. Critical mass of splenic autotransplant needed for the development of phagocytic activity in rats. Clin Exp Immunol 2012; 170:77-85. [PMID: 22943203 DOI: 10.1111/j.1365-2249.2012.04632.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
When total splenectomy is inevitable, heterotopic splenic autotransplantation seems to be the only alternative to maintain the functions of the spleen. The present study was carried out to analyse the critical mass of splenic autotransplant (SAT) for the development of phagocytic activity in rats. Wistar rats were submitted to total splenectomy (TS) alone or in combination with slices of SAT ranging from an average rate of 21·9% (one slice) to 100% (five slices) of the total splenic mass implanted into the greater omentum. Sixteen weeks after the beginning of the experiment, the animals were inoculated intravenously with a suspension of Escherichia coli labelled with Tc-99m. After 20 min, the rats were killed and the liver, lung and spleen or SAT, as well as blood samples were removed to determine the percentage of labelled bacteria uptake in these tissues. As the percentage of the total splenic mass contained in the SAT increased, the bacteria remaining in the blood decreased. From the implant of 26% up to the implant of the total splenic mass (100%) there was no difference in the bacteria remaining in the blood between the healthy animals of the control group and those submitted to TS combined with SAT. This finding shows that the critical mass needed for the development of phagocytic activity of macrophages in splenic autotransplants in adult rats is 26% of the total splenic mass.
Collapse
Affiliation(s)
- R G Marques
- Department of General Surgery, Pedro Ernesto University Hospital, Rio de Janeiro, Brazil.
| | | | | | | | | | | | | | | |
Collapse
|
|
8
|
Tissue factor-factor VIIa complex induces epithelial ovarian cancer cell invasion and metastasis through a monocytes-dependent mechanism. Int J Gynecol Cancer 2011; 21:616-24. [PMID: 21543928 DOI: 10.1097/igc.0b013e3182150e98] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE Tumor-associated macrophage infiltration and up-regulation of tissue factor-factor VII (TF-FVIIa) complex have been observed in the peritoneum and stroma of epithelial ovarian cancer (EOC). However, it is not clear how tumor-associated macrophage and TF-FVIIa complex promotes EOC invasion. In the present study, we aimed to determine the mechanism by which interaction of TF-FVIIa and monocytes (MOs) promotes EOC metastasis. METHOD Matrigel invasion assay was used to analyze the potential of EOC metastasis. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to detect expressions of cytokines and chemokines. Fluorescence-activated cell sorting was used to count the percentage of CD14, CD68, and CD163 of MOs. RESULTS We found that the TF-FVIIa complex caused dynamic changes in MOs cytokine and chemokine expression. CD14 and CD163 were also upregulated on MOs by TF-FVIIa. Epithelial ovarian cancer cells were cocultured with TF-FVIIa-stimulated MOs, demonstrating increased invasion potential. Interleukin 8 (IL-8) was proposed as the major chemoattractant mediating EOC invasion based on MOs messenger RNA and protein expression profiles. Anti-IL-8 monoclonal neutralizing antibody attenuated EOC cell invasion in a concentration-dependent manner, and tumor necrosis factor α from TF-FVIIa-stimulated MOs was observed to amplify IL-8 production. The following transcription factors in MOs were activated by TF-FVIIa and inhibited by the tissue factor pathway inhibitor: oncogenes HIF-1α, HIF-1β, Oct I, Oct II, and Egr-1; inflammatory mediators c-Fos and c-Rel; and STAT family members STAT5A and STAT5B. CONCLUSIONS Our study suggested that the interaction between the TF-FVIIa complex might play a role in mediating EOC invasion and metastasis depending on MOs mechanism.
Collapse
|
|
9
|
Lu J, Zhao J, Zhao J, Ma J, Liu K, Yang H, Huang Y, Qin Z, Bai R, Li P, Yan W, Zhao M, Dong Z. VEGF-A-induced immature DCs not mature DCs differentiation into endothelial-like cells through ERK1/2-dependent pathway. Cell Biochem Funct 2011; 29:294-302. [DOI: 10.1002/cbf.1752] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2010] [Revised: 02/14/2011] [Accepted: 02/18/2011] [Indexed: 11/08/2022]
|
|
10
|
Zhang T, Ma Z, Wang R, Wang Y, Wang S, Cheng Z, Xu H, Jin X, Li W, Wang X. Thrombin facilitates invasion of ovarian cancer along peritoneum by inducing monocyte differentiation toward tumor-associated macrophage-like cells. Cancer Immunol Immunother 2010; 59:1097-108. [PMID: 20352429 PMCID: PMC11030270 DOI: 10.1007/s00262-010-0836-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2009] [Accepted: 02/16/2010] [Indexed: 01/26/2023]
Abstract
Peritoneal metastasis is a distinct pathologic characteristic of advanced epithelial ovarian cancer (EOC), which is the most deadly disease of the female reproductive tract. The inflammatory environment of the peritoneum in EOC contains abundant macrophages, activated thrombin, and thrombin-associated receptors. However, little is known about the mechanism by which the thrombin-macrophages interaction contributes to tumor invasion and metastasis. We investigated the phenotype and cytokine/chemokine expression of thrombin-treated peripheral blood monocytes (MOs)/macrophages, it was found that the phenotype of MOs was altered toward a TAM-like macrophage CD163(high)IL-10(high)CCL18(high)IL-8(high) after thrombin stimulation. By Matrigel invasion assay, the conditioned medium of thrombin-stimulated MOs accelerated remarkable invasion of ES-2, SKOV3, and HO-8910, which was similar to invasive cell numbers of ascites stimuli (P < 0.05) and higher than MOs medium alone (P < 0.05). IL-8 was proposed as the major chemoattractant mediating EOC invasion based on MOs mRNA and protein expression profiling. It was observed that anti IL-8 monoclonal neutralizing antibody attenuated EOC cell invasion in a concentration-dependent manner. Increased transcriptional activation of NF-kappaB p50/p65 was identified in thrombin-treated MOs. This study provided insight the role of thrombin in the regulation of EOC peritoneal invasion via "educating" MOs.
Collapse
Affiliation(s)
- Ting Zhang
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001 China
| | - Zhengwen Ma
- Department of Neurobiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Ruili Wang
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001 China
| | - Ying Wang
- Department of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200023 China
| | - Shujun Wang
- Department of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200023 China
| | - Zhongping Cheng
- Department of Obstetrics and Gynecology, Shanghai Yangpu Central Hospital, Shanghai, 200090 China
| | - Hong Xu
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001 China
| | - Xinjuan Jin
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001 China
| | - Weiping Li
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001 China
| | - Xipeng Wang
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001 China
| |
Collapse
|
|
11
|
Lu J, Zhao J, Liu K, Zhao J, Yang H, Huang Y, Qin Z, Bai R, Li P, Ma J, Yan W, Zhao M, Dong Z. MAPK/ERK1/2 signaling mediates endothelial-like differentiation of immature DCs in the microenvironment of esophageal squamous cell carcinoma. Cell Mol Life Sci 2010; 67:2091-106. [PMID: 20221785 PMCID: PMC11115913 DOI: 10.1007/s00018-010-0316-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2009] [Revised: 02/09/2010] [Accepted: 02/15/2010] [Indexed: 10/19/2022]
Abstract
Endothelial-like differentiation of dendritic cells (DCs) is a new phenomenon, and the mechanism is still elusive. Here, we show that the tumor microenvironment derived from the human esophageal squamous cell carcinoma (ESCC) cell line EC9706 can induce immature DCs (iDCs) differentiate toward endothelial cells, and become endothelial-like cells, but it has no obvious influence on mature DCs. During the course of endothelial-like differentiation of iDCs, a sustained activation of mitogen-activated protein kinase/extracelluar signal-regulated kinase1/2 (MAPK/ERK1/2) and cAMP response element-binding protein (CREB) was detected. Incubation of iDCs with MEK phosphorylation inhibitor PD98059 blocked the MAPK/ERK1/2 and CREB phosphorylation as well as the endothelial-like differentiation of iDCs. Inhibition of vascular endothelial growth factor-A (VEGF-A) in the microenvironment with its antibody blocked the endothelial-like differentiation and the phosphorylation of MAPK/ERK1/2 and CREB. These data suggest that MAPK/ERK1/2 signaling pathway activated by VEGF-A could mediate endothelial-like differentiation of iDCs in the ESCC microenvironment.
Collapse
Affiliation(s)
- Jing Lu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
12
|
The interaction of coagulation factor XII and monocyte/macrophages mediating peritoneal metastasis of epithelial ovarian cancer. Gynecol Oncol 2010; 117:460-6. [PMID: 20233624 DOI: 10.1016/j.ygyno.2010.02.015] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2009] [Revised: 02/10/2010] [Accepted: 02/13/2010] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Pathological studies have indicated that the peritoneum of epithelial ovarian cancer (EOC) patients exhibits characteristics of chronic inflammation like peritonitis. Abundant macrophage infiltration and increased expression of coagulation factor XII (FXII) have been observed in the peritoneum of EOC patients. The aim of this study is to determine how the interaction between FXII and monocyte/macrophages (MO/MAs) contributes to EOC cell invasion and metastasis of the peritoneum. METHODS MO/MAs from the peripheral blood of healthy female donors and tumor-associated macrophages (TAMs) from EOC ascites were collected and cultured. We assessed phenotypes, cytokine/chemokine production, and phagocytic function of FXII-treated MO/MAs. The effects of the FXII-MO/MAs interaction on EOC cell invasion were determined by the Matrigel in vitro invasion assay. In addition, signaling pathway mediators were evaluated for their potential roles in MO/MA activation. RESULTS MO/MAs exhibited M2-polarized phenotypes after FXII treatment, which was CD163(high)IL-10(high)CCL18(high)IL-8(high)CCR2(high)CXCR2(high). The phagocytic potential of MO/MAs was also upregulated. Matrigel results indicated that invasion of EOC cells was enhanced when exposed to conditioned medium from FXII-stimulated MO/MAs. Transcription factors found to be upregulated in FXII-stimulated MO/MAs included Fra-1, Fra-2, Fos-B in the AP-1 family, oncogenes HIF-1 and Oct, and STAT-5A in the STAT family. CONCLUSIONS FXII may facilitate EOC cell metastasis by transforming MO/MAs toward tumor-associated macrophage-like cells.
Collapse
|
|
13
|
Diesen DL, Zimmerman SA, Thornburg CD, Ware RE, Skinner M, Oldham KT, Rice HE. Partial splenectomy for children with congenital hemolytic anemia and massive splenomegaly. J Pediatr Surg 2008; 43:466-72. [PMID: 18358283 DOI: 10.1016/j.jpedsurg.2007.10.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Partial splenectomy is an alternative to total splenectomy for the treatment of congenital hemolytic anemias (CHAs) in children, although the feasibility of this technique in the setting of massive splenomegaly is unknown. This study was designed to evaluate the safety and efficacy of partial splenectomy in children with CHAs and massive splenomegaly. This retrospective study examined 29 children with CHAs who underwent partial splenectomy. Children were divided into 2 groups based on splenic size: 8 children had splenic volumes greater than 500 mL, whereas 21 children had splenic volumes less than 500 mL. Outcome variables included perioperative complications, transfusion requirements, hematocrits, reticulocyte counts, bilirubin levels, splenic sequestration, and splenic regrowth. All 29 children underwent successful partial splenectomy with 0.02 to 10 years of follow-up. After partial splenectomy, children overall had decreased transfusion requirements, increased hematocrits, decreased bilirubin levels, decreased reticulocyte counts, and elimination of splenic sequestration. Children with massive splenomegaly had similar outcomes compared with children without massive splenomegaly. Long-term complications included 3 mild infections, 4 cases of gallstones requiring cholecystectomy, and 1 child who required completion splenectomy. Partial splenectomy is a safe, effective, and technically feasible option for children with various CHAs, even in the setting of massive splenomegaly.
Collapse
Affiliation(s)
- Diana L Diesen
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Zhang SJ, Zhang H, Hou M, Zheng Z, Zhou J, Su W, Wei Y, Hu S. Is it possible to obtain "true endothelial progenitor cells" by in vitro culture of bone marrow mononuclear cells? Stem Cells Dev 2007; 16:683-90. [PMID: 17784841 DOI: 10.1089/scd.2006.0062] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
In vitro-cultured bone marrow cells have been shown to contain some low-density lipoprotein (LDL) uptake-positive cells. Although a small portion of LDL uptake-positive cells had expression for endothelial markers, all of them demonstrated a phagocytosis function similar to monocyte/macrophages and expression of the panleukocyte surface marker CD45 and monocyte marker CD14. These LDL uptake-positive cells did not show significant proliferative capacity and died out gradually in long-term culture. In contrast, the bone marrow-derived LDL uptake-negative cells showed strong proliferation and expression of typical mesenchymal surface markers CD29 and CD44. Although cultured under endothelial promoting conditions, these mesenchymal stem cells (MSCs) did not show any sign of differentiation toward endothelial cells. In conclusion, adult bone marrow-derived LDL uptake-positive cells that have been reported so far actually are monocytes/macrophages that can express some endothelial markers but are not "true endothelial progenitor cells" (EPCs). MSCs, which are the only cell type that shows strong proliferation during long-term adherent culture for bone marrow cells, do not differentiate toward the endothelial lineage when grown under endothelial promoting conditions.
Collapse
Affiliation(s)
- Shi Ju Zhang
- Research Center for Cardiovascular Regenerative Medicine, Ministry of Health, and Department of Cardiovascular Surgery, Cardiovascular Institute and Fu-Wai Hospital, PUMC and CAMS, Beijing, 100037, China
| | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Godiris-Petit G, Goasguen N, Munoz-Bongrand N, Cattan P, Sarfati E. Splénectomie partielle par laparoscopie et ultracision©. ACTA ACUST UNITED AC 2007; 144:339-41. [DOI: 10.1016/s0021-7697(07)91966-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
16
|
Cytokine production during the inhibition of acute vascular rejection in a concordant hamster-to-rat cardiac xenotransplantation model. Chin Med J (Engl) 2007. [DOI: 10.1097/00029330-200701020-00015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
|
|
17
|
Zhang SJ, Zhang H, Wei YJ, Su WJ, Liao ZK, Hou M, Zhou JY, Hu SS. Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture. Cell Res 2006; 16:577-84. [PMID: 16775629 DOI: 10.1038/sj.cr.7310075] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Mononuclear cells (MNCs) isolated from peripheral blood by density gradient centrifugation were plated on human fibronectin-coated culture plates and cultured in EGM-2 medium. Attached spindle-shaped cells, reported as endothelial progenitor cells (EPCs) by some investigators, had elongated from adherent round cells, but had not proliferated from a small number of cells as supposed previously. The growth curve of the primary EPCs showed that the cells had little proliferative capacity. Flow cytometry analysis showed that the cells could express some of the endothelial lineage markers, while they could also express CD14, which is considered a marker of monocyte/macrophage lineages throughout culture. In endothelial function assays, the cells demonstrated a lower level of expression of eNOS than mature endothelial cells in the reverse transcription-polymerase chain reaction and did not show an ability to develop tube-like structures in angiogenesis assay in vitro. In this study, we identified the monocytoid function of EPCs by the combined Dil-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and Indian ink uptake tests. All the cells were double positive for Dil-Ac-LDL and Indian ink uptake at days 4, 14 and 28 of culture, which means the EPCs maintained monocytoid function throughout the culture. Therefore, although adult EPCs from peripheral MNCs have some endothelial lineage properties, they maintain typical monocytic function and have little proliferative capacity.
Collapse
Affiliation(s)
- Shi Ju Zhang
- Research Center for Cardiovascular Regenerative Medicine, Ministry of Health, West District, Beijing 100037, China
| | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Torres MB, Vega VL, Bedri M, Saad D, Trentzsch H, Reeves RH, De Maio A. IL-10 Plasma Levels are Elevated After LPS Injection in Splenectomized A/J Mice1. J Surg Res 2005; 129:101-6. [PMID: 16087192 DOI: 10.1016/j.jss.2005.06.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2005] [Revised: 05/09/2005] [Accepted: 06/08/2005] [Indexed: 11/20/2022]
Abstract
BACKGROUND Splenectomy is clinically indicated in certain cases of hypersplenism and splenic trauma. However, it is associated with serious complications, in particular, reduced clearance of encapsulated organisms and a high incidence of sepsis, which has been coined overwhelming post-splenectomy sepsis (OPSS). In addition to the role of the spleen in the clearance of microorganisms, this organ may be involved in regulation of the inflammatory response. We investigated the effect of splenectomy on the inflammatory process induced by LPS in a murine model that resembles, in part, the pathophysiological aspects of sepsis. MATERIALS AND METHODS Male mice (8-weeks-old) from different inbred strains were randomized into three groups: splenectomized (SPX), sham operated (SHAM), and non-operated controls (NoOp). After 9 days of recovery, mice were injected with LPS (15 mg/kg) and cytokine plasma levels were measured by ELISA at 1.5 or 6 h after injection. Peritoneal macrophages (PMphi) were isolated from the three groups, and cytokine production was evaluated after incubation with LPS in culture conditions. RESULTS IL-10 plasma levels were elevated in SPX A/J mice (6.7 +/- 0.4 mug/ml) after injection of LPS (15 mg/kg) compared to NoOp A/J mice (4.2 +/- 0.2 mug/ml, P < 0.05). Similar elevation in IL-10 plasma levels was detected in SPX DBA/2J mice as compared to NoOp DBA/2J mice, but not in C57BL/6J and BALB/cJ mice. In contrast, SPX AKR mice displayed lower IL-10 levels than NoOp mice. PMphis from SPX A/J mice produced elevated levels of IL-10 compared to PMphis from SHAM or NoOp A/J mice, mimicking the in vivo observations. CONCLUSION Our data suggest that the spleen plays an important role in modulating the inflammatory process induced by LPS, extending beyond passive clearance of encapsulated organisms. In addition, the contribution of the spleen to the inflammatory process may be influenced by the genetic background.
Collapse
Affiliation(s)
- Manuel B Torres
- Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
| | | | | | | | | | | | | |
Collapse
|
|
19
|
Brandt CT, Leite CRC, Manhaes-de-Castro R, Brandt Filho C, Manhaes-de-Castro FM, Barbosa-de-Castro CMM. Avaliação do efeito da esplenectomia e auto-implante esplênico sobre algumas funções de monócitos em crianças com esquistossomose mansônica. Rev Soc Bras Med Trop 2005; 38:38-42. [PMID: 15717093 DOI: 10.1590/s0037-86822005000100008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Investigamos em portadores de esquistossomose hepatoesplênica após esplenectomia com ou sem auto-implante esplênico: índice de aderência, produção de superóxido (SP) e de TNF-alfa em monócitos, tratados ou não com tuftsina. Avaliamos três grupos: voluntários sadios CG (grupo controle) (n=12); esplenectomizados com auto-implante AG (n=18) e esplenectomizados sem auto-implante WAG (n=9). Índice de aderência e TNF-alfa não diferiram entre os grupos. SP foi semelhante em CG e AG na 1ª hora após estimulação celular. SP foi maior em todos intervalos de tempo nos grupos CG e AG, comparados ao WAG. O tratamento com tuftsina recuperou o padrão de normalidade de SP em AG, com aumento da 1ª para a 2ª hora nos níveis do CG. O tratamento com tuftsina não alterou SP em WAG, permanecendo reduzida em todos intervalos. O auto-implante esplênico parece recuperar e manter os parâmetros imunológicos avaliados, que têm participação importante na resposta do hospedeiro às infecções.
Collapse
Affiliation(s)
- Carlos T Brandt
- Departamento de Cirurgia, Universidade Federal de Pernambuco, Recife, PE
| | | | | | | | | | | |
Collapse
|
|
20
|
Bessler H, Bergman M, Salman H, Beilin B, Djaldetti M. The relationship between partial splenectomy and peripheral leukocyte count. J Surg Res 2004; 122:49-53. [PMID: 15522314 DOI: 10.1016/j.jss.2004.05.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2004] [Indexed: 11/21/2022]
Abstract
BACKGROUND Partial splenectomy is accepted as a treatment modality for hypersplenism permitting preservation of the spleen functions. Since a prominent leukocytosis is a marked event after total splenectomy, it was the aim of the present study to compare the peripheral white blood cell counts (PWBC) and immune response in mice following partial and total splenectomy. MATERIALS AND METHODS Four groups of animals were included in the study: mice in which 70% of the spleen was removed, animals that underwent total splenectomy, mice with sham operation, and a group of mice that served as controls. The proliferative response of peripheral blood mononuclear cells, peritoneal cells, and splenocytes was examined using concavalin (Con) A. RESULTS In distinction from marked leukocytosis observed in mice after total splenectomy, in partially splenectomized mice the PWBC counts did not show any significant increase during a follow-up period of up to 2 months after surgery. The mitogen response of the mononuclear cells to Con A in partially splenectomized mice was similar to that of controls, while in animals after total splenectomy, it was increased in cells from the peripheral blood and decreased in those from the peritoneum. CONCLUSIONS The results indicate that removal of as much as about 70% of the spleen in mice is sufficient to maintain a normal PWBC count, suggesting a regulatory role of the spleen remnant on the PWBC production. The normal mitogen response of the cells to Con A indicates that the spleen rudiment preserves at least a part of the immune activity of the intact spleen.
Collapse
Affiliation(s)
- Hanna Bessler
- The Laboratory for Immunology and Hematology Research, Rabin Medical Center-Golda Campus, Petah-Tiqva and the Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel
| | | | | | | | | |
Collapse
|
|
21
|
Brandt CT, Leite CRC, Manhães-de-Castro R, Brandt Filho C, Castro CMMBD. Aderência e atividade microbicida de monócitos em portadores de esquistossomose mansônica na forma hepatoesplênica cirúrgica. Acta Cir Bras 2003. [DOI: 10.1590/s0102-86502003000200011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
A cirurgia nas crianças portadoras de esquistossomose mansônica inclui esplenectomia, ligadura da veia gástrica esquerda e o auto-implante de tecido esplênico no omento maior. A eficácia desse procedimento pode ser responsável pelo desaparecimento da sepse fulminante pós-esplenectomia (SFPE) neste tipo de paciente. Esta condição é atribuída à diminuição de IgM, de linfócitos circulantes, de properdina e ausência de tuftsina, o que conduz a deficiência da atividade das células macrófágicas, que são responsáveis pela aderência à bactéria, fagocitose e destruição das mesmas. OBJETIVO: Analisar os aspectos funcionais dos monócitos destes pacientes, operados quando crianças, no Serviço de Cirurgia Geral da Criança do Hospital das Clínicas da UFPE, entre 1991 a 2000. MÉTODOS: Foram analisados os índices de aderência in vitro dos monócitos e a geração do ânion superóxido (O2-), em três grupos. O 1º, auto-implante (AI), constituído por 18 portadores de esquistossomose mansônica na forma hepatoesplênica, submetidos a esplenectomia, ligadura da veia gástrica esquerda e auto-implante de tecido esplênico no omento maior; o 2º, (ESP), formado por nove pacientes similares, submetidos a esplenectomia e desconexão ázigo-portal, e o 3º,(CT), constituído por 12 adolescentes sadios, oriundos da mesma condição sócio-econômica-geográfica. RESULTADOS: Não houve diferença no índice de aderência entre os três grupos. Os monócitos dos pacientes do grupo AI tiveram a geração de O2- semelhante à dos indivíduos do grupo CT, e significantemente maior do que os pacientes do grupo ESP. CONCLUSÕES: Os monócitos dos portadores de esquistossomose hepatoesplênica submetidos a esplenectomia, ligadura da veia gástrica esquerda e auto-implante de tecido esplênico no omento maior se mostram funcionalmente similares aos de indivíduos normais da mesma condição sócio-econômica-geográfica.
Collapse
|
|
22
|
Abstract
BACKGROUND Partial splenectomy is indicated for benign tumors and cysts of the spleen, as well as, operative management of splenic trauma limited to one pole of the spleen. Despite improved technique, bleeding from the cut surface of the spleen still remains an obstacle. METHODS We describe our technique for partial splenectomy using a new device based on coupling saline with radiofrequency energy to achieve hemostasis while dividing the splenic parenchyma. RESULTS Use of this technique has led to blood loss of less than 50 cc, while achieving splenic preservation.
Collapse
Affiliation(s)
- Vic Velanovich
- Division of General Surgery, K-8, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
| | | |
Collapse
|
|
23
|
Abstract
AIM: To evaluate the clinical application of serial operations with preservation of spleen.
METHODS: Serial operations with preserving spleen were performed on 211 cases in our hospital from 1980 to 2000. The patient’s age ranged from 13 to 56 years, averaging 38 years. Diseases included splenic injury in 171 cases, portal hypertension in 9 cases, splenic cyst in 10 cases, and the lesion of pancreatic body and tail in 21 cases.
RESULTS: All the cases were cured, and 129 patients were followe dup from 3 mo to 3 years with the leukocyte phagocytosis test, detection of immunoglubin, CT, 99mTc scanning and ultrasonography. The results were satisfactory.
CONCLUSION: The operations with preserving spleen were safe, feasible, and worth of clinical application.
Collapse
Affiliation(s)
- H C Jiang
- Department of General Surgery, First Clinical Hospital, Harbin Medical University, Harbin 150001, China
| | | | | | | | | | | |
Collapse
|