PLASMA FIBRONECTIN IN PLATELET HEMOSTATIC FUNCTION

血小板在止血和血栓栓塞性疾病中发挥核心作用， 部分彼此粘附（聚集）或血管壁粘附（粘附）。 这些反应部分是通过与一类大型生物的相互作用来介导的 二硫键连接的糖蛋白。 我们发现凝血酶诱导 这些糖蛋白之一纤连蛋白的特异性和可饱和结合 (fn)血小板。 根据我们的初步数据，我们设想 FN与血小板的相互作用涉及以下四个步骤 下面 静息细胞大于FN结合位点II大于Fn 结合III大于Fn加工IV大于功能。 我们将 剖析并定义反应中的每一个步骤 顺序 反应I描述了FN结合位点的诱导， 血小板刺激 我们将确定哪些刺激会，哪些不会 使用分泌和非分泌刺激支持FN结合。 的 将研究选定药物对FN结合的影响， 定义了结合位点诱导所需的生化途径。 反应II需要fn与血小板结合。 的影响 环境条件，如温度、pH和二价离子，将被 已建立，血小板识别的FN结构域 将被定义。 此外，将采用多种方法来确定 FN的结合位点。 将特别强调以下方面的作用： 纤维蛋白（原）在FN结合中的作用。 反应III 需要处理血小板结合的fn，我们将研究 通过转氨酶使血小板表面上的FN交联，或 二硫键，fn的内化，以及与 细胞骨架成分 反应IV涉及以下功能性后果： fn与血小板结合，无论是初始结合的结果，还是 后续处理。 其对血小板聚集和粘附的影响， 血凝块收缩和单核细胞-血小板相互作用可能代表 将被探索的候选事件。

Platelets play a central role in hemostasis and thromboembolic disease, in part adherence to each other (aggregation) or vessel walls (adhesion). These reactions are mediated in part by interactions with a class of large disulfide-linked glycoproteins. We have found that thrombin induces specific and saturable binding of one of these glycoproteins, fibronectin (fn) to platelets. Based on our preliminary data, we envision the interaction of fn with the platelet to involve the four steps diagrammed below. Resting Cell greater than FN Binding Site II greater than Fn Binding III greater than Fn Processing IV greater than Functional. We will dissect and define each of these individual steps in the reaction sequence. Reaction I describes the induction of the fn binding site by platelet stimulation. We shall identify stimuli which do and do not support fn binding using both secretory and non secretory stimuli. The effect of selected drugs on fn binding will be investigated as a means of defining biochemical pathways required for binding site induction. Reaction II entails fn binding to the platelet. The effect of environmental conditions such as temperature, pH and divalent ions, will be established, and the domains of fn which are recognized by the platelet will be defined. In addition, multiple approaches will be used to identify the binding site for fn. Particular emphasis will be given to the role of fibrin(ogen) in fn binding based on our preliminary data. Reaction III entails processing of platelet-bound fn, and we shall investigate cross-linking of fn on the platelet surface via transglutaminases or disulfide bonding, internalization of fn, and interactions with cytoskeletal elements. Reaction IV involves the functional consequences of fn binding to the platelet, either as a result of initial binding or subsequent processing. Its effect on platelet aggregation and adhesion, clot retraction and monocyte-platelet interaction represent likely candidate events which will be explored.