SICKLE CELL-ENDOTHELIAL INTERACTIONS AND VASOOCCLUSION

拟议的研究将集中在镰状（SS）红细胞-内皮细胞 相互作用和相关的血管阻塞 技术和活体观察。我们将调查 镰状细胞病中红细胞与内皮细胞的异常相互作用 通过强调明确的血流动力学、细胞和 体液因素实验旨在实现以下目标 目的：1.血流动力学因素在确定出血部位和出血部位中的作用 与壁剪切率和微血管相关的粘附程度 粘附位点以及粘附和红细胞聚集对 血流动力学参数2.血管性血友病因子（vWF）的作用，其他 粘附蛋白，以及这些蛋白的已知受体， 抑制镰状细胞-内皮相互作用。3.定义基础 对于所观察到的密度定义的 镰状细胞的种类为了区分细胞刚性的作用， （脱氧和MCHC）和膜特性的粘附 密度定义的SS细胞类别。3.为了调查选定的 血管活性刺激在粘连中的作用。重点将放在以下方面的作用： 在内皮中引起多种反应的物质（例如， 组胺、缓激肽、凝血酶等），从而影响vWF分泌， 微静脉通透性以及血管张力。另外， 将评价已知的平滑肌激动剂和松弛剂。结果 拟议的议定书可能提供更好的理解的潜力， 粘附在镰状细胞病血管闭塞事件中的作用

The proposed research will focus on sickle (SS) red cell-endothelial interaction and related vasoocclusion using a combination of perfusion techniques and intravital observations. We will investigate the basis of abnormal red cell interaction with the endothelium in sickle cell disease by emphasizing the potential role of defined hemodynamic, cellular and humoral factors. Experiments are designed to accomplish the following objectives: 1. The role of hemodynamic factors in determining the sites and extent of adhesion with reference to the wall shear rates and microvascular adhesion sites and the effect of adhesion and red cell aggregation on hemodynamic parameters. 2. The role of von Willebrand factor (vWF), other adhesive proteins, and known receptors to these proteins in promotion and inhibition of sickle cell-endothelial interaction. 3. To define the basis for the observed differences in adhesion properties of density-defined classes of sickle cells. To differentiate the role of cellular rigidity (deoxygenation and MCHC) and membrane characteristics in adhesion of density defined SS cell classes. 3. To investigate the role of selected vasoactive stimuli in adhesion. Emphasis will be given to the role of substances which elicit multiple responses in the endothelium (e.g. , histamine, bradykinin, thrombin, etc) and thereby effect the vWF secretion, venular permeability as well as the vascular tone. Also, the effect of known smooth muscle agonists and relaxants will be evaluated. The results of the proposed protocol may provide better understanding of the potential role of adhesion in vasooclusive events in sickle cell disease.