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.
Novel Vascular Molecule Involved in Monocyte Adhesion to Aortic Endothelium in Models of Atherogenesis
Address correspondence to Leslie M. McEvoy, Department of Pathology, L235, Stanford University, Stanford, CA 94305.
L.M. McEvoy was a Senior Fellow of the American Heart Association, California Division, and the National Multiple Sclerosis Society during part of this work. H. Sun is supported by Public Health Service grant No. CAO9302 and a predoctoral award from the National Cancer Institute. P.S. Tsao was the recipient of a National Service Research Award. J.P. Cooke was a recipient of the Vascular Academic Award from the National Heart, Lung, and Blood Institute. This work was supported by grants from the National Institutes of Health and the Core Facilities of the Stanford Digestive Disease Center under DK38707.
1Abbreviations used in this paper: GPI, glycosylphosphatidylinositol; HDL, high density lipoprotein; HEV, high endothelial venules; ICAM, intracellular adhesion molecule; MM-LDL, minimally modified LDL; PI-PLC, phosphatidylinositol-specific phospholipase; MAdCAM, mucosal addressin cell adhesion molecule; PP, Peyer's patch; RAEC, rabbit aortic endothelial cells; RT, room temperature; VCAM, vascular cell adhesion molecule; VMAP-1, vascular monocyte adhesion-associated protein 1.
Leslie M. McEvoy, Hailing Sun, Philip S. Tsao, John P. Cooke, Judith A. Berliner, Eugene C. Butcher; Novel Vascular Molecule Involved in Monocyte Adhesion to Aortic Endothelium in Models of Atherogenesis. J Exp Med 16 June 1997; 185 (12): 2069–2077. doi: https://doi.org/10.1084/jem.185.12.2069
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