VON WILLEBRAND FACTOR AND PLATELET-MEDIATED HEMOSTASIS

血管性血友病因子和血小板介导的止血

• 批准号: 3339398
• 负责人: EDWARD P KIRBY
• 金额: $ 13.81万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-05-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3339398
• 关键词: affinity chromatography; affinity labeling; autoradiography; cell adhesion; centrifugation; chemical binding; chemical group; chemical synthesis; coagulation factor VIII; conformation; electron microscopy; gel electrophoresis; hemostasis; high performance liquid chromatography; human tissue; monoclonal antibody; mucopolysaccharides; platelet aggregation; platelets; proteolysis; thrombosis; vascular endothelium

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.

von Willebrand因子（VWF）是一个大的等离子体糖蛋白 血小板识别并结合受损的内皮所必需 表面。 牛VWF以某种方式直接与人类血小板结合 是人VWF与血小板相互作用的模型 下皮表面。 该项目的目标是：（a）确定VWF的区域 分子负责与血小板结合，胶原蛋白的结合， 和糖胺聚糖，（b）识别VWF的血小板受体 并确定VWF与血小板结合的机制，以及（c）与 描述VWF结合对代谢反应的影响 血小板，相反，其他激动剂对血小板的影响 对VWF的响应。 VWF分子上的功能域将被识别，并 由VWF，化学和 VWF的酶促修饰，并通过使用单克隆抗体对VWF。 VWF的血小板受体将通过亲和色谱分离 并且还将通过光性标签在原位识别。 血小板 通过测量VWF结合，聚合将研究响应能力 反应，形状变化和血小板释放反应。 改变 血小板蛋白标记将受到监测，并分布 激活和未激活血小板上的受体将通过 电子显微镜，具有偶共轭的特定探针的受体。 这些研究应该更好地了解基本机制 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形成并发症 患病或受损的血管或人造表面（例如 假体心脏瓣膜，透析膜或血管假体。