PLATELET PROCOAGULANT ACTIVITY AND C3/C5-ACTIVATION

补体蛋白C3和C5的蛋白水解性激活 已知与血栓形成有关，以及 经典和替代补体途径的激活物 可促进血小板分泌，加速血液凝结。这个 这项提案中描述的研究旨在推导出分子 导致C3和C5蛋白分解激活的途径 刺激的血小板表面，并研究其作用 C3/C5-转换酶反应在血小板促凝剂表达中的作用 活动。在这个项目中，我们将使用凝胶过滤的人血小板 和纯化的人类补体和凝血蛋白 实验中的系统，目的是：1)识别哪些组件 AP或CP转换酶反应直接启动血小板 血小板凝血酶原酶活性的分泌和表达；2) 识别与血小板有关的信号转导途径 C3/C5-转换酶或其激活介导的触发 产品；3)确定C3b的拓扑分布 血小板表面及其与血小板活化的关系；4) 以推断血小板活化改变血管紧张素转换酶的机制 对CP和AP C3/C5-转换酶的调控 细胞表面；5)确定补体如何激活 在采集和储存血小板期间自发发生的 因为输血会影响血小板功能和促凝剂 活动。有人建议，从这些数据中获得的数据 实验将极大地帮助我们理解 细胞组装酶反应的相互关系 补体和止血系统。

Proteolytic activation of complement proteins C3 and C5 is known to occur in association with thrombus formation, and activators of both classical and alternative complement pathways can initiate platelet secretion and accelerate blood clotting. The research described in this Proposal aims to deduce the molecular pathways leading to proteolytic activation of C3 and C5 at the surface of stimulated platelets, and to investigate the role of the C3/C5-convertase reaction in expression of platelet procoagulant activity. In this Project we will use gel-fil-tered human platelets and purified proteins of the human complement and coagulation systems in experiments that aim: 1) to identify which components of the AP or CP convertase reaction directly initiate platelet secretion and expression of platelet prothrombinase activity; 2) to identify the signal-transduction pathways involved in platelet triggering mediated by C3/C5-convertases or their activated products; 3) to determine the topological distribution of C3b on the platelet surface, and its relationship to platelet activation; 4) to deduce the mechanism by which platelet activation alters the regulatory control of the CP and AP C3/C5-convertases at the cell surface ; 5) to determine how complement activation occurring spontaneously during collection and storage of platelets for transfusion affects platelet function and procoagulant activity. It is proposed that the data obtained from these experiments will significantly contribute to our understanding of the interrelationships of the cell-assembled enzyme reactions of the complement and hemostatic systems.