Nature Immunology3, 151 - 158 (2002)
Published online: 14 January 2002; | doi:10.1038/ni755
JAM-1 is a ligand of the 2 integrin LFA-1 involved in transendothelial migration of leukocytes
Georg Ostermann1, 2, Kim S. C. Weber1, Alma Zernecke1, Andreas Schröder1
& Christian Weber1, 2
1
Institute for Prevention of Cardiovascular Diseases, Ludwig-Maximilians-University, Munich, Germany.
2
Department of Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule, Pauwelsstrasse 30, 52074 Aachen, Germany.
Correspondence should be addressed to Christian Weber cweber@ukaachen.de
Inflammatory recruitment of leukocytes is governed by dynamic interactions between integrins and endothelial immunoglobulin superfamily (IgSF) proteins. We have identified the IgSF member junctional adhesion molecule 1 (JAM-1) as a ligand of the 2 integrin lymphocyte function−associated antigen 1 (LFA-1). Under static and physiological flow conditions, JAM-1 contributed to LFA-1−dependent transendothelial migration of T cells and neutrophils as well as LFA-1−mediated arrest of T cells. The latter was triggered by chemokines on endothelium that was stimulated with cytokines to redistribute JAM-1 from the tight junctions. Transfectants expressing JAM-1 supported LFA-1−mediated adhesion of leukocytes, which required the membrane-proximal Ig-like domain 2 of JAM-1. Thus, JAM-1 is a counter-receptor for LFA-1 that is ideally situated to guide and control transmigration during leukocyte recruitment.
2 integrin LFA-1 involved in transendothelial migration of leukocytes
2 integrin lymphocyte function−associated antigen 1 (LFA-1). Under static and physiological flow conditions, JAM-1 contributed to LFA-1−dependent transendothelial migration of T cells and neutrophils as well as LFA-1−mediated arrest of T cells. The latter was triggered by chemokines on endothelium that was stimulated with cytokines to redistribute JAM-1 from the tight junctions. Transfectants expressing JAM-1 supported LFA-1−mediated adhesion of leukocytes, which required the membrane-proximal Ig-like domain 2 of JAM-1. Thus, JAM-1 is a counter-receptor for LFA-1 that is ideally situated to guide and control transmigration during leukocyte recruitment.
