title: JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes.
abstract: 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.
authors.affiliation: Institute for Prevention of Cardiovascular Diseases, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ostermann
authors.forename: Kim S C
authors.initials: KS
authors.lastname: Weber
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröder
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000818:Animals; D001665:Binding Sites; D018821:CD18 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019169:Jurkat Cells; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018821:CD18 Antigens; C515255:CXCL12 protein, human; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C407243:F11R protein, human; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D013755:Tetradecanoylphorbol Acetate