CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin VLA-6.
Regulated adherence of polymorphonuclear leukocytes (PMNs) to endothelium and subendothelial matrix is a critical event for PMN localization at and migration into inflammatory sites. We previously reported that human PMNs stimulated in vitro adhere to laminin, the major glycoprotein of mammalian basement membrane, by both CD11/CD18 (beta 2 integrin)-dependent and CD11/CD18-independent mechanisms. This CD11/CD18-independent adherence is inhibited by monoclonal antibodies (MoAbs) directed against the beta 1 subunit of integrins (very late antigens [VLA]). The specific PMN VLA receptor responsible for stimulated CD11/CD18-independent PMN adherence to laminin was not elucidated. We show here that this CD11/CD18-independent adherence is mediated by a member of the beta 1 integrins, VLA-6. MoAbs GoH3 and 450-30, which bind the alpha 6 subunit of VLA-6, significantly reduced adherence of phorbol myristate acetate-stimulated PMNs to laminin-coated surfaces when CD11/CD18-independent adherence was blocked with anti-CD11/CD18 MoAbs. Furthermore, GoH3 completely inhibited stimulated adherence of CD11/CD18-deficient PMNs to laminin. Analysis by flow cytometry showed that human PMNs express VLA-6. The PMN alpha 6 is identical in size and pl to the platelet alpha 6, but the PMN beta 1 exhibits considerable heterogeneity in molecular weight compared with the platelet beta 1. This activation-dependent adherence receptor for laminin may play a role in PMN interaction with basement membrane laminin during PMN movement through vascular walls.
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
J F
JF
Bohnsack
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D005434:Flow Cytometry; D006801:Humans; D007797:Laminin / Q000502:physiology*; D051379:Mice; D008970:Molecular Weight; D009504:Neutrophils / Q000502:physiology*; D011233:Precipitin Tests; D051381:Rats; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D007797:Laminin; D016029:Receptors, Very Late Antigen