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Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum‐mediated but complement‐independent mechanisms

Summary An increased number of apoptotic bodies have been detected in glomeruli of non‐nephritic kidneys of C1q‐deficient mice. In these mice an in vivo impaired uptake of apoptotic cells by peritoneal macrophages was also demonstrated. Here we investigated whether C1q plays a role in the in vitro c...

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Published in:Clinical and experimental immunology 2002-12, Vol.130 (3), p.459-466
Main Authors: CORTES‐HERNANDEZ, J., FOSSATI‐JIMACK, L., CARUGATI, A., POTTER, P. K., WALPORT, M. J., COOK, H. T., BOTTO, M.
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creator CORTES‐HERNANDEZ, J.
FOSSATI‐JIMACK, L.
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BOTTO, M.
description Summary An increased number of apoptotic bodies have been detected in glomeruli of non‐nephritic kidneys of C1q‐deficient mice. In these mice an in vivo impaired uptake of apoptotic cells by peritoneal macrophages was also demonstrated. Here we investigated whether C1q plays a role in the in vitro clearance of apoptotic cells by glomerular mesangial cells. Phagocytosis was assessed using a novel flow cytometric assay that was validated by immunofluorescence studies. The uptake of apoptotic cells by mesangial cells, measured as percentage of mesangial cells ingesting apoptotic cells, was ∼25%, 10% and 10% for a T cell lymphoma line (RMA), thymocytes and neutrophils, respectively. The uptake reached a plateau phase after 3 h, was specific for apoptotic cells and was mediated by serum but not by complement components C1q or C3. The phagocytosis of apoptotic cells was significantly inhibited by Arg‐Gly‐Asp‐Ser (RGDS), a peptide capable of blocking the interaction of thrombospondin with CD36 or the vitronectin receptor. Pretreatment of the mesangial cells with dexamethasone (200 nm) but not with LPS increased the uptake markedly. These findings indicate that murine mesangial cells are capable of taking up syngeneic apoptotic cells, although much less efficiently than professional phagocytic cells. They also show that serum proteins other than complement components mediate the removal of apoptotic cells by murine mesangial cells in vitro.
doi_str_mv 10.1046/j.1365-2249.2002.01998.x
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They also show that serum proteins other than complement components mediate the removal of apoptotic cells by murine mesangial cells in vitro.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1046/j.1365-2249.2002.01998.x</identifier><identifier>PMID: 12452836</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Ageing, cell death ; Animals ; Apoptosis ; Basic Immunology ; Biological and medical sciences ; Blood Proteins - metabolism ; Cell physiology ; complement ; Complement C1q ; Complement C3 ; Dexamethasone - pharmacology ; Flow Cytometry ; Fundamental and applied biological sciences. 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K.</creatorcontrib><creatorcontrib>WALPORT, M. J.</creatorcontrib><creatorcontrib>COOK, H. T.</creatorcontrib><creatorcontrib>BOTTO, M.</creatorcontrib><title>Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum‐mediated but complement‐independent mechanisms</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Summary An increased number of apoptotic bodies have been detected in glomeruli of non‐nephritic kidneys of C1q‐deficient mice. In these mice an in vivo impaired uptake of apoptotic cells by peritoneal macrophages was also demonstrated. Here we investigated whether C1q plays a role in the in vitro clearance of apoptotic cells by glomerular mesangial cells. Phagocytosis was assessed using a novel flow cytometric assay that was validated by immunofluorescence studies. 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They also show that serum proteins other than complement components mediate the removal of apoptotic cells by murine mesangial cells in vitro.</description><subject>Ageing, cell death</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Basic Immunology</subject><subject>Biological and medical sciences</subject><subject>Blood Proteins - metabolism</subject><subject>Cell physiology</subject><subject>complement</subject><subject>Complement C1q</subject><subject>Complement C3</subject><subject>Dexamethasone - pharmacology</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. 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T.</au><au>BOTTO, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum‐mediated but complement‐independent mechanisms</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2002-12</date><risdate>2002</risdate><volume>130</volume><issue>3</issue><spage>459</spage><epage>466</epage><pages>459-466</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>Summary An increased number of apoptotic bodies have been detected in glomeruli of non‐nephritic kidneys of C1q‐deficient mice. In these mice an in vivo impaired uptake of apoptotic cells by peritoneal macrophages was also demonstrated. Here we investigated whether C1q plays a role in the in vitro clearance of apoptotic cells by glomerular mesangial cells. Phagocytosis was assessed using a novel flow cytometric assay that was validated by immunofluorescence studies. The uptake of apoptotic cells by mesangial cells, measured as percentage of mesangial cells ingesting apoptotic cells, was ∼25%, 10% and 10% for a T cell lymphoma line (RMA), thymocytes and neutrophils, respectively. The uptake reached a plateau phase after 3 h, was specific for apoptotic cells and was mediated by serum but not by complement components C1q or C3. The phagocytosis of apoptotic cells was significantly inhibited by Arg‐Gly‐Asp‐Ser (RGDS), a peptide capable of blocking the interaction of thrombospondin with CD36 or the vitronectin receptor. Pretreatment of the mesangial cells with dexamethasone (200 nm) but not with LPS increased the uptake markedly. These findings indicate that murine mesangial cells are capable of taking up syngeneic apoptotic cells, although much less efficiently than professional phagocytic cells. They also show that serum proteins other than complement components mediate the removal of apoptotic cells by murine mesangial cells in vitro.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12452836</pmid><doi>10.1046/j.1365-2249.2002.01998.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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1365-2249
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subjects Ageing, cell death
Animals
Apoptosis
Basic Immunology
Biological and medical sciences
Blood Proteins - metabolism
Cell physiology
complement
Complement C1q
Complement C3
Dexamethasone - pharmacology
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Glomerular Mesangium - cytology
Glomerular Mesangium - drug effects
Glucocorticoids - pharmacology
Leukocytes
mesangial cell
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular and cellular biology
Neutrophils
Oligopeptides - pharmacology
Phagocytosis
Stimulation, Chemical
Tumor Cells, Cultured
title Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum‐mediated but complement‐independent mechanisms
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