THE ROLE OF MEMBRANE PROTEINS IN PLATELET FUNCTION

动脉血栓形成是疾病和死亡的主要原因。在……现场 血管疾病，血小板聚集并构成血管疾病的主要组成部分 这些血栓。血栓周边的血小板可能破裂。 离开和返回循环，这个可逆的激活反应 可能会导致显著的细胞膜变化。这项提议的目的是 检查可能由血小板引起的四种特殊的膜变化 激活：肌动蛋白聚合导致膜变形性降低， 这种不太容易变形的膜的碎裂会导致 膜微粒，内源性分泌蛋白的表面结合， 膜结合免疫球蛋白的变化。我们的实验将测量 这些变化(A)在凝血酶激活后和(B)在 全血的自发凝血，我们将在体外将它们联系起来 对慢性阻塞性肺疾病患者的血小板和血浆的研究结果 血栓性疾病。将测量血小板肌动蛋白的聚合度 通过抑制右旋糖核酸酶。血小板膜微粒 将通过使用单抗的放射免疫分析来定量测定血浆中的 针对固有的膜糖蛋白的抗体。的结合部位 膜表面内源性分泌蛋白及其在细胞周期调控中的作用 将对血小板粘附性进行定义。激活对细胞周期的影响 血小板免疫球蛋白浓度及其亚细胞分布 研究，特别是研究唾液酸损失的可能性 在血小板激活过程中可能会导致免疫球蛋白与去唾液酸糖蛋白结合 IB是一种自然发生的自体移植的“衰老抗原” 抗体。可能导致多个可逆的血小板接触相互作用 在聚合肌动蛋白增加的情况下，膜逐渐丧失 物质和免疫球蛋白的积累。这可能会发生在 作为内皮支持的功能的正常循环导致 衰老血小板的结构和功能变化。这些循环 血栓患者的可逆相互作用可能会加速 疾病及循环血小板膜变化的测定 应该允许认识到那些有更高风险的患者 血栓形成。

Arterial thrombosis is a major cause of illness and death. At the site of the vessel disease, blood platelets aggregate and form a major component of these thrombi. The platelets on the periphery of the thrombus may break away and return to the circulation, and this reversible activation reaction could result in significant membrane changes. The aim of this proposal is to examine four specific membrane changes which may result from platelet activation: actin polymerization causing decreased membrane deformability, fragmentation of this less deformable membrane to cause the loss of membrane microparticles, surface binding of endogenous secreted proteins, and changes of membrane-bound immunoglobulin. Our experiments will measure these changes (a) following activation by thrombin and (b) during the spontaneous clotting of whole blood, and we will correlate these in vitro results with studies of the platelets and plasma from patients with thrombotic disease. The polymerization of platelet actin will be measured by dexoyribonuclease inhibition. Microparticles of the platelet membrane will be quantified in plasma by a radioimmunoassay using a monoclonal antibody to an intrinsic membrane glycoprotein. The binding sites of endogenous secreted proteins on the membrane surface and their role in platelet adhesion will be defined. The effect of activation on the platelet IgG concentration and its subcellular distribution will be studied, specifically investigating the possibility that sialic acid loss during platelet activation may lead to IgG binding, with asialoglycoprotein Ib being a "senescent antigen" for naturally occurring autologous antibodies. Multiple reversible platelet contact interactions may result in an increase of polymerized actin, a progressive loss of membrane material, and the accumulation of immunoglobulin. This could occur in the normal circulation as a function of endothelial support causing the structural and functional changes of senescent platelets. These cycles of reversible interactions could be accelerated in patients with thrombotic disease, and measurement of these membrane changes of circulating platelets should allow the recognition of patients who have an increased risk for thrombosis.