JAM-1 is a ligand of the [beta]2 integrin LFA-1 involved in transendothelial migration of leukocytes

• Published in: Nature immunology Vol. 3; no. 2; p. 151
• Main Authors: Ostermann, Georg, Weber, Kim S C, Zernecke, Alma, Schröder, Andreas, Weber, Christian
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 01-02-2002
• Subjects: Adhesion; Lymphocytes; Physiology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni755

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 beta(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.