Adhesion molecules mediate diverse cellular responses in a variety of fundamental physiological processes, including embryogenesis and development, wound-healing, and host defense against foreign antigens and microorganisms. Adhesion molecules on blood cells and the vessel wall are critically involved in the pathogenesis of a variety of clinical disorders ranging from autoimmune and inflammatory diseases to cancer metastasis. Atherosclerotic lesion formation results from an excessive, inflammatory-fibroproliferative response to various forms if insult to the artery wall. Adhesive interactions between blood cells and the vessel are pivotal in the recruitment of leukocytes in the inflammatory component of atherogenesis and also participate in the sentinel clinical event of plaque rupture and thrombosis: This proposal examines selected aspects of these adhesive interactions in the following three specific aims: 1) To Determine the Mechanisms by which Post-Receptor Events Regulate Leukocyte beta1-Integrin-Dependent Adhesion; 2) To examine 'Outside- In' Signaling by the Endothelial Adhesion Receptor VCAM-1; and 3) To Examine the Mechanisms and Consequences of Platelet-Endothelial Interactions In Vitro and In Vivo.
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