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The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment
The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that RAGE functions as an endothelial adhesion receptor promoting leukocyte recruitment. In an animal model of thioglycol...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194124/ https://www.ncbi.nlm.nih.gov/pubmed/14623906 http://dx.doi.org/10.1084/jem.20030800 |
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author | Chavakis, Triantafyllos Bierhaus, Angelika Al-Fakhri, Nadia Schneider, Darius Witte, Steffen Linn, Thomas Nagashima, Mariko Morser, John Arnold, Bernd Preissner, Klaus T. Nawroth, Peter P. |
author_facet | Chavakis, Triantafyllos Bierhaus, Angelika Al-Fakhri, Nadia Schneider, Darius Witte, Steffen Linn, Thomas Nagashima, Mariko Morser, John Arnold, Bernd Preissner, Klaus T. Nawroth, Peter P. |
author_sort | Chavakis, Triantafyllos |
collection | PubMed |
description | The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that RAGE functions as an endothelial adhesion receptor promoting leukocyte recruitment. In an animal model of thioglycollate-induced acute peritonitis, leukocyte recruitment was significantly impaired in RAGE-deficient mice as opposed to wild-type mice. In diabetic wild-type mice we observed enhanced leukocyte recruitment to the inflamed peritoneum as compared with nondiabetic wild-type mice; this phenomenon was attributed to RAGE as it was abrogated in the presence of soluble RAGE and was absent in diabetic RAGE-deficient mice. In vitro, RAGE-dependent leukocyte adhesion to endothelial cells was mediated by a direct interaction of RAGE with the β2-integrin Mac-1 and, to a lower extent, with p150,95 but not with LFA-1 or with β1-integrins. The RAGE–Mac-1 interaction was augmented by the proinflammatory RAGE-ligand, S100-protein. These results were corroborated by analysis of cells transfected with different heterodimeric β2-integrins, by using RAGE-transfected cells, and by using purified proteins. The RAGE–Mac-1 interaction defines a novel pathway of leukocyte recruitment relevant in inflammatory disorders associated with increased RAGE expression, such as in diabetes, and could provide the basis for the development of novel therapeutic applications. |
format | Text |
id | pubmed-2194124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21941242008-04-11 The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment Chavakis, Triantafyllos Bierhaus, Angelika Al-Fakhri, Nadia Schneider, Darius Witte, Steffen Linn, Thomas Nagashima, Mariko Morser, John Arnold, Bernd Preissner, Klaus T. Nawroth, Peter P. J Exp Med Article The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that RAGE functions as an endothelial adhesion receptor promoting leukocyte recruitment. In an animal model of thioglycollate-induced acute peritonitis, leukocyte recruitment was significantly impaired in RAGE-deficient mice as opposed to wild-type mice. In diabetic wild-type mice we observed enhanced leukocyte recruitment to the inflamed peritoneum as compared with nondiabetic wild-type mice; this phenomenon was attributed to RAGE as it was abrogated in the presence of soluble RAGE and was absent in diabetic RAGE-deficient mice. In vitro, RAGE-dependent leukocyte adhesion to endothelial cells was mediated by a direct interaction of RAGE with the β2-integrin Mac-1 and, to a lower extent, with p150,95 but not with LFA-1 or with β1-integrins. The RAGE–Mac-1 interaction was augmented by the proinflammatory RAGE-ligand, S100-protein. These results were corroborated by analysis of cells transfected with different heterodimeric β2-integrins, by using RAGE-transfected cells, and by using purified proteins. The RAGE–Mac-1 interaction defines a novel pathway of leukocyte recruitment relevant in inflammatory disorders associated with increased RAGE expression, such as in diabetes, and could provide the basis for the development of novel therapeutic applications. The Rockefeller University Press 2003-11-17 /pmc/articles/PMC2194124/ /pubmed/14623906 http://dx.doi.org/10.1084/jem.20030800 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Chavakis, Triantafyllos Bierhaus, Angelika Al-Fakhri, Nadia Schneider, Darius Witte, Steffen Linn, Thomas Nagashima, Mariko Morser, John Arnold, Bernd Preissner, Klaus T. Nawroth, Peter P. The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment |
title | The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment |
title_full | The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment |
title_fullStr | The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment |
title_full_unstemmed | The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment |
title_short | The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment |
title_sort | pattern recognition receptor (rage) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194124/ https://www.ncbi.nlm.nih.gov/pubmed/14623906 http://dx.doi.org/10.1084/jem.20030800 |
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