RED CELL ADHERENCE TO ENDOTHELIUM IN SICKLE CELL DISEASE

镰状细胞病（SS-D）的发病率和死亡率 是由血管紧张素Ⅱ引起的组织缺血和梗塞引起的。 闭塞最近的证据表明， 镰状红细胞（RBC）到血管内皮可能 导致了这些血管闭塞事件的目标 计划的研究是描述分子机制 参与镰状红细胞对血管的异常粘附 内皮细胞用于定义RBC的体外系统- 内皮细胞相互作用包括静态和动态 使用分离自人的内皮细胞培养物的粘附测定 血管内皮细胞和红细胞，血小板和血浆分离自 患有SS-D的患者具体目标是：1）识别 RBC-内皮细胞特性的差异，或 内皮下基质粘附，将静态条件与 控制流的条件，2）研究RBC的作用 粘附分子并表征RBC亚群 具有增强的粘合性能，3）为了检查 粘附性血浆蛋白、细胞外基质蛋白和 红细胞粘附中的内皮细胞粘附分子，以及4） 研究血小板在RBC-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了解 红细胞-内皮细胞相互作用的分子机制 在止血功能，不仅在SS-D，而且在正常 生理学和其他与血管闭塞相关的疾病 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.