Novel vascular molecule involved in monocyte adhesion to aortic endothelium in models of atherogenesis.
Adhesion of monocytes to the endothelium in lesion-prone areas is one of the earliest events in fatty streak formation leading to atherogenesis. The molecular basis of increased monocyte adhesion is not fully characterized. We have identified a novel vascular monocyte adhesion-associated protein, VMAP-1, that plays a role in adhesion of monocytes to activated endothelium. Originally selected for its ability to block binding of a mouse monocyte-like cell line (WEHI78/24) to cytokine- or LPS-stimulated cultured mouse endothelial cells in vitro, antiVMAP-1 mAb LM151 cross-reacts with rabbit endothelium and blocks binding of human monocytes to cultured rabbit aortic endothelial cells stimulated with minimally modified low density lipoprotein, thought to be a physiologically relevant atherogenic stimulus. Most importantly, LM151 prevents adhesion of normal monocytes and monocytoid cells to intact aortic endothelium from cholesterol-fed rabbits in an ex vivo assay. VMAP-1 is a 50-kD protein. Immunohistology of vessels reveals focal constitutive expression in aorta and other large vessels. VMAP-1 is thus a novel vascular adhesion-associated protein that appears to play a critical role in monocyte adhesion to aortic endothelial cells in atherogenesis in vivo.
McEvoy
L M
LM
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, Stanford, California 94305, USA.
Sun
H
H
Tsao
P S
PS
Cooke
J P
JP
Berliner
J A
JA
Butcher
E C
EC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000209:etiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000502:physiology*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D008070:Lipopolysaccharides