PROTHROMBIN ACTIVATION ON BLOOD MONONUCLEAR CELLS

单核/巨噬细胞在炎症和动脉粥样硬化中起关键作用 过程，在某些情况下，在血管外组织进行 其特征是广泛的纤维蛋白沉积和 纤维增生反应。 由于凝血酶是一种有效的效应物， 这些反应，总的假设是，凝血酶生产在 单核细胞/巨噬细胞表面提供重要的生物调节 在这些位点的效应分子。 目标是定义 控制分子事件的结合和动力学参数， 导致凝血酶在单核细胞/巨噬细胞表面表达 并开始阐明调节细胞内 促凝血表型的表达。 特别强调 关于单核细胞/巨噬细胞表面膜如何调节凝血酶原酶 复杂的组装和功能，通过表达结合位点， 辅因子因子Va和酶因子XA以及的表达 膜结合蛋白酶，其激活原辅因子因子Va， 因子Va。该项目的总体目标是提供一个详细的 了解凝血酶的产生是如何影响和调节的， 单核细胞表面通过一系列整体相关的事件。的 在单核细胞/巨噬细胞表面凝血酶的形成似乎是 这些细胞的生理和病理生理功能 当它们定位于血管和血管外组织部位时提供。

Monocytes/macrophages play key roles in inflammatory and atherosclerotic processes, which in several instances proceed at extravascular tissue sites and are characterized by extensive fibrin deposition and a fibroproliferative response. Since thrombin is a potent effector of these responses, the overall hypothesis is that thrombin production at the monocyte/macrophage surface provides an important bioregulatory effector molecule at these sites. The objectives are to define the binding and kinetic parameters governing the molecular events which result in the expression of thrombin at the monocyte/macrophage surface and begin to elucidate the cellular mechanisms which regulate the expression of a procoagulant phenotype. Particular emphasis is placed on how the monocyte/macrophage surface membrane regulates prothrombinase complex assembly and function through the expression of binding sites for the cofactor factor Va and the enzyme factor Xa, and the expression of membrane-bound proteases which activate the procofactor factor Va to factor Va. The overall goal of this project is to provide a detailed understanding of how thrombin generation is effected and regulated at the monocyte surface through a series of integrally related events. The formation of thrombin at the monocyte/macrophage surface appears to be pivotal to the physiological and pathophysiological functions these cells provide as they localize to vascular and extravascular tissue sites.