BLOOD CELL/ENDOTHELIAL ADHESIVE INTERACTIONS

黏附分子在多种基本生理过程中介导多种细胞反应，包括胚胎发生和发育、伤口愈合以及宿主对外来抗原和微生物的防御。血细胞和血管壁上的粘附分子在多种临床疾病的发病机制中起着至关重要的作用，从自身免疫性疾病和炎症性疾病到癌症转移。动脉粥样硬化病变的形成是由于对各种形式的动脉壁损伤产生过度的炎症-纤维增生反应。在动脉粥样硬化的炎症成分中，血细胞和血管之间的粘附相互作用是白细胞募集的关键，也参与斑块破裂和血栓形成的前哨临床事件。本提案在以下三个具体目标中研究了这些粘附相互作用的选定方面：1)确定受体后事件调节白细胞β -整合素依赖性粘附的机制；2)内皮粘附受体VCAM-1的“外-内”信号传导；3)在体外和体内研究血小板-内皮相互作用的机制和后果。

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.