RED CELL ADHERENCE TO ENDOTHELIUM IN SICKLE CELL DISEASE

镰状细胞病(SS-D)的大部分发病率和死亡率 是由血管引起的组织缺血和梗塞引起的 遮挡。最近的证据表明，一种异常的坚持 镰刀状红细胞(RBC)对血管内皮细胞的影响 导致这些血管闭塞事件。的目标是 计划中的研究将描述分子机制。 参与镰状红细胞与血管的异常黏附 内皮细胞。用于定义RBC的体外系统- 内皮细胞的相互作用将包括静态和动态 用分离的人内皮细胞进行黏附实验 血管内皮细胞、红细胞、血小板和血浆的分离 SS-D患者。具体目标是：1)识别 红细胞内皮细胞或红细胞特性的差异 内皮下基质黏附，比较静态条件和 可控流动的条件，2)研究红细胞的作用 黏附分子(S)与红细胞亚群特征(S) 具有增强的粘接性能，3)检查 黏附血浆蛋白、细胞外基质蛋白和 内皮细胞黏附分子在红细胞黏附中的作用，以及4)与 研究血小板在红细胞-内皮细胞相互作用中的作用。 这项研究的长期目标是更好地理解 红细胞-内皮细胞相互作用的分子机制 在止血功能上，不仅在SS-D，而且在正常 与血管闭塞相关的生理学和其他疾病 并发症。

Much of the morbidity and mortality of sickle cell disease (SS-D) is caused by tissue ischemia and infarction due to vascular occlusion. Recent evidence suggests that an abnormal adherence of sickle red blood cells (RBCs) to vascular endothelium may contribute to these vaso-occlusive events. The goal of the projected research is to characterize the molecular mechanisms involved in the abnormal adherence of sickle RBCs to vascular endothelial cells. The in vitro systems used to define the RBC- endothelial cell interactions will include both static and dynamic adhesion assays using endothelial cell cultures isolated from human vascular endothelium, and RBCs, platelets and plasma isolated from patients with SS-D. The specific aims are: 1) To identify differences in the characteristics of RBC-endothelial cell or subendothelial matrix adhesion, comparing static conditions to conditions of controlled flow, 2) To investigate the role of RBC adhesion molecule(s) and characterize the subpopulation(s) of RBCs with enhanced adhesive properties, 3) To examine the role of adhesive plasma proteins, extracellular matrix proteins and endothelial cell adhesive molecules in RBC adhesion, and 4) To study the role of platelets in RBC-endothelial cell interactions. The Iong-term goal of this research is to better understand the molecular mechanisms involved in RBC-endothelial cell interactions in the function of hemostasis, not only in SS-D, but also in normal physiology and other diseases associated with vaso-occlusive complications.