PLATELET ANTIGENS AND PLATELET ACTIVATION

血小板抗原和血小板激活

• 批准号: 6161520
• 负责人: H GRALNICK
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161520
• 关键词: aplastic anemia; atherosclerosis; clinical research; endotoxins; exercise; granule; human subject; human tissue; method development; monoclonal antibody; paroxysmal nocturnal hemoglobinuria; phosphatidylinositols; platelet activation; platelets; thrombocytopenia; von Willebrand's disease

We have developed several methods to study platelet activation ex vivo and in vitro. These studies were made possible by the development and implementation of techniques to isolate platelets from human blood without inducing platelet activation or secretion. We have developed nine monoclonal antibodies that react only with activated platelets. Our results have shown that in some forms of von Willebrand's disease, platelet activation is present and causes thrombocytopenia. In patients with arteriosclerotic heart disease, platelet activation is increased after exercise. This finding suggests that some endotoxin, spontaneous platelet activation or enhances agonist-induced platelet activation is not observed. Exercise in individuals with minor or mild atherosclerosis does not induce platelet activation. We have identified patients with paroxysmal nocturnal hemoglobinuria (PNM) platelet activation. The activation was shown by release of alpha granule protein and increased fibrinogen binding to the platelet surface. New evidence of coagulation activation was observed. These findings suggest that platelet activation may be the primary mechanism of venous thrombosis in PNH. Studies to test this hypothesis are being implemented.

我们已经开发了几种方法来研究离体血小板活化， 体外这些研究之所以成为可能， 实施从人血中分离血小板的技术， 诱导血小板活化或分泌。我们开发了九个 单克隆抗体只与活化的血小板反应。我们 结果显示在某些形式的血管性血友病中， 存在血小板活化并引起血小板减少症。患者 动脉粥样硬化性心脏病，血小板活化增加， 锻炼后。这一发现表明，一些内毒素，自发 血小板活化或增强激动剂诱导的血小板活化不是 观察轻度或轻微动脉粥样硬化患者的运动 不诱导血小板活化。 我们已经确定了阵发性睡眠性血红蛋白尿症（PNM）患者 血小板活化激活表现为α颗粒的释放 蛋白质和增加的纤维蛋白原结合到血小板表面。新 观察到凝血活化的证据。这些发现表明 血小板活化可能是静脉血栓形成的主要机制 在PNH。正在实施测试这一假设的研究。