PLATELETS AND BLOOD FLOW IN SICKLE CELL DISEASE

镰状细胞病中的血小板和血流

• 批准号: 2445315
• 负责人: Theodore Wun
• 金额: $ 9.95万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-13 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2445315
• 关键词: cell adhesion; conjunctiva; erythrocytes; fibronectins; flow cytometry; fluorescent dye /probe; human subject; intravital microscopy; microcirculation; monoclonal antibody; platelet activation; platelet aggregation; receptor; sickle cell anemia; thrombospondins

Vascular occlusive events account for much of the morbidity and mortality in patients with sickle cell disease. The pathogenesis of these vaso- occlusive events remains ill-defined and the subject of much speculation. The focus of this research proposal will be the role of platelet activation and platelet-erythrocyte aggregates in vaso-occlusive events. We hypothesize the following: 1) There is baseline platelet activation in patients with sickle cell disease which increases during vaso-occlusive crisis, 2) increased platelet activation is negatively correlated with blood flow in the microvasculature, 3) circulating platelet-erythrocyte aggregates (PEA) are present in patients with sickle cell disease and increase during vaso-occlusive events and, 4) platelet-erythrocyte aggregation is mediated by thrombospondin and fibronectin. Using fluorescent-labeled antibodies to activation-dependent and -independent platelet antigens, red cell antigens, and flow cytometry, longitudinal studies of patients with sickle cell disease will be done to determine the degree of platelet activation and platelet-erythrocyte aggregate formation and their relation to clinical events. Platelet activation and PEA will be correlated with blood flow as measured by computer-assisted intravital microscopy of the bulbar conjunctiva. The role of fibronectin and thrombospondin in PEA formation will be studied by the incubation of platelets and red cells from patients and normals, in the presence and absence of antibodies to these adhesive proteins or their receptors. These data will fill gaps in the knowledge of the degree arid persistence of platelet activation, microcirculatory blood flow abnormalities, and platelet-red cell interactions in sickle call patients.

血管闭塞事件占发病率和死亡率的大部分 在镰状细胞病患者中。 这些血管- 闭塞事件仍然定义不清，是许多猜测的主题。 这项研究提案的重点将是血小板的作用 活化和血小板-红细胞聚集。 我们假设：1）基线血小板活化， 镰状细胞病患者在血管闭塞期间增加 危机，2）血小板活化增加与 微脉管系统中的血流，3）循环血小板-红细胞 聚集体（PEA）存在于镰状细胞病患者中， 血管闭塞事件期间增加，4）血小板-红细胞 聚集由血小板反应蛋白和纤连蛋白介导。 使用 荧光标记的抗激活依赖性和非激活性抗体 血小板抗原、红细胞抗原和流式细胞术，纵向 将对镰状细胞病患者进行研究， 血小板活化程度和血小板-红细胞聚集体形成 及其与临床事件的关系。血小板活化和PEA将 与通过计算机辅助活体内测量的血流量相关 球结膜显微镜检查。纤维连接蛋白的作用， 血小板反应蛋白在PEA形成中的作用将通过孵育 血小板和红细胞的患者和正常人，在存在和 缺乏针对这些粘附蛋白或其受体的抗体。这些 数据将填补知识的空白， 血小板活化、微循环血流异常，以及 镰状细胞患者血小板-红细胞相互作用。