{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:45:59Z","timestamp":1791409559613,"version":"4.3.3"},"reference-count":35,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11,17]]},"abstract":"<jats:p>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 \u03b22-integrin Mac-1 and, to a lower extent, with p150,95 but not with LFA-1 or with \u03b21-integrins. The RAGE\u2013Mac-1 interaction was augmented by the proinflammatory RAGE-ligand, S100-protein. These results were corroborated by analysis of cells transfected with different heterodimeric \u03b22-integrins, by using RAGE-transfected cells, and by using purified proteins. The RAGE\u2013Mac-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.<\/jats:p>","DOI":"10.1084\/jem.20030800","type":"journal-article","created":{"date-parts":[[2003,11,17]],"date-time":"2003-11-17T22:17:51Z","timestamp":1069107471000},"page":"1507-1515","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":496,"title":["The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins"],"prefix":"10.1084","volume":"198","author":[{"given":"Triantafyllos","family":"Chavakis","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine I, University Heidelberg, D-69115 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Bierhaus","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine I, University Heidelberg, D-69115 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Al-Fakhri","sequence":"additional","affiliation":[{"name":"5Institute for Clinical Chemistry, Justus-Liebig-University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Schneider","sequence":"additional","affiliation":[{"name":"3Third Department of Internal Medicine, Justus-Liebig-University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Witte","sequence":"additional","affiliation":[{"name":"2Institute for Medical Biometry and Informatics, University Heidelberg, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Linn","sequence":"additional","affiliation":[{"name":"3Third Department of Internal Medicine, Justus-Liebig-University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Nagashima","sequence":"additional","affiliation":[{"name":"7Berlex Biosciences, Richmond, CA 94806"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Morser","sequence":"additional","affiliation":[{"name":"7Berlex Biosciences, Richmond, CA 94806"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Arnold","sequence":"additional","affiliation":[{"name":"6Department of Molecular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus T.","family":"Preissner","sequence":"additional","affiliation":[{"name":"4Institute for Biochemistry, Justus-Liebig-University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Nawroth","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine I, University Heidelberg, D-69115 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,11,17]]},"reference":[{"key":"2023072512065241400_BIB1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0092-8674(94)90337-9","volume":"76","year":"1994","journal-title":"Cell."},{"key":"2023072512065241400_BIB2","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1182\/blood.V84.7.2068.2068","volume":"84","year":"1994","journal-title":"Blood."},{"key":"2023072512065241400_BIB3","doi-asserted-by":"crossref","first-page":"21785","DOI":"10.1074\/jbc.R000003200","volume":"275","year":"2000","journal-title":"J. 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