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。 血小板识别和结合受损内皮细胞所需 表面。牛vWF直接与人血小板结合的方式 是人类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、胶原结合的分子， 和糖胺多聚糖，(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vWF结合对新陈代谢反应的影响 血小板，相反，其他激动剂对血小板的影响 对vWF的响应能力。 VWF分子上的功能结构域将被识别并 以vWF的蛋白水解性碎片为特征，通过化学和 VWF的酶修饰，以及利用抗vWF的单抗。 将通过亲和层析分离vWF的血小板受体 并将通过光亲和标记进行原位鉴定。血小板 响应性将通过测量vWF结合、聚集 反应、形态改变和血小板释放反应。中的更改 将监测血小板蛋白标记和分布 激活的和未激活的血小板上的受体将通过 用金标记的受体特异性探针的电子显微镜。 这些研究应该能更好地理解基本机制。 潜在的血小板对血管损伤部位的识别。他们 可能会提出新的方法来处理相关的血栓并发症 有病变或受损的血管或人造表面，如 人工心脏瓣膜、透析膜或血管假体。

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.