VON WILLEBRAND FACTOR AND PLATELET-MEDIATED HEMOSTASIS

血管性血友病因子（vWF）是一种大的血浆糖蛋白， 血小板识别并结合受损内皮细胞所需的 表面。 牛vWF直接与人血小板结合， 是人vWF与血小板相互作用的模型， 内皮下表面。 该项目的目标是：（a）确定vWf的区域 负责与血小板、胶原蛋白 和糖胺聚糖，（B）鉴定vWF的血小板受体 并确定vWF与血小板结合的机制，以及（c） 描述了vWF结合对代谢反应的影响， 血小板，以及相反地，其他激动剂对血小板的作用。 对vWF的反应性。 将鉴定vWF分子上的功能结构域， 其特征在于vWF的蛋白水解片段化，通过化学和 vWF的酶促修饰，以及通过使用vWF的单克隆抗体。 将通过亲和色谱法分离vWF的血小板受体 并且也将通过光亲和标记原位鉴定。 血小板 将通过测量vWF结合、聚集 反应、形状变化和血小板释放反应。 的改变 将监测血小板蛋白标记， 活化和非活化血小板上的受体将通过 电子显微镜与金结合的受体特异性探针。 这些研究应能更好地了解 血小板对血管损伤部位的潜在识别。 他们 可能为治疗血栓性并发症提供新的方法， 具有患病或受损的血管或具有人造表面， 人工心脏瓣膜、透析膜或人造血管。

von Willebrand Factor (vWF) is a large plasma glycoprotein which is required for platelets to recognize and bind to damaged endothelial surfaces. Bovine vWF binds directly to human platelets in a manner which is a model for the interaction of human vWF with platelets on subendothelial surfaces. The goals of the project are: (a) to identify the regions of the vWf molecule which are responsible for its binding to platelets, to collagen, and to glycosaminoglycans, (b) to identify the platelet receptor for vWF and determine the mechanism by which vWF binds to platelets, and (c) to describe the effects of vWF binding on the metabolic responses of the platelets, and, conversely, the effects of other agonists on platelet responsiveness to vWF. The functional domains on the vWF molecule will be identified and characterized by proteolytic fragmentation of the vWF, by chemical and enzymatic modification of vWF, and by use of monoclonal antibodies to vWF. The platelet receptor for vWF will be isolated by affinity chromatography and will also be identified in situ by photoaffinity labeling. Platelet responsiveness will be studied by measuring vWF binding, aggregation responses, shape change and the platelet release reaction. Alterations in platelet protein labeling will be monitored and the distribution of receptors on activated and non-activated platelets will be visualized by electron microscopy with gold-conjugated specific probes for the receptors. These studies should provide a better understanding of the basic mechanisms underlying platelet recognition of sites of damage in blood vessels. They may suggest new ways to deal with the thrombotic complications associated with diseased or damaged blood vessels or with artificial surfaces such as prosthetic heart valves, dialysis membranes, or vascular prostheses.