ACTIVATED ENDOTHELIAL ADHESIVITY IN SC VASOOCCLUSION

描述：（改编自研究者摘要）本提案的重点是 内皮细胞对与镰状细胞有密切关系的激动剂的粘附反应 细胞疾病具体目的是检验以下假设：1） 凝血酶和缺氧（I/R）可增强内皮细胞对SS RB粘附性; 2）特异性EC 粘合剂分子导致粘合性增加;以及3）可识别的 细胞机制解释了增加的粘附性。目标1和2将是 在体外和体内使用镰状细胞病小鼠模型进行研究。的 对激活的内皮细胞粘附性的独特关注提供了一种创新的 这个建议的前景。转基因敲除镰刀的可用性 细胞小鼠模型与人类疾病高度一致， 最先进活体显微镜系统提供了一种特殊的 有机会在体内验证体外粘附现象的重要性。 这些实验有望增强我们对分子生物学的理解。 镰状红细胞-内皮细胞粘附的机制，提高我们对 镰状细胞血管闭塞的病理生理学，并扩大我们对 内皮细胞生物学它们可能为未来的治疗提供基础。 干预措施。

DESCRIPTION: (Adapted from investigator's abstract) This proposal focuses on the adhesogenic responses of endothelial cells to agonists germane to sickle cell disease. The specific aims are to test the following hypotheses: 1) that thrombin and hypoxia (I/R) enhance EC adhesivity for SS RB; 2) that specific EC adhesive molecules account for increased adhesivity; and 3) that identifiable cellular mechanisms account for the increased adhesivity. Aims 1 and 2 will be studied in vitro and, using a mouse model of sickle cell disease, in vivo. The singular focus on activated endothelial cell adhesivity provides an innovative perspective to this proposal. The availability of a transgenic knockout sickle cell mouse model highly concordant with the human disease and of a state-of-the-art intravital microscopy system provide an exceptional opportunity to verify in vivo the importance of in vitro adherence phenomena. These experiments are anticipated to enhance our understanding of the molecular mechanisms of sickle erythrocyte-endothelial adherence, improve our grasp of the pathophysiology of sickle cell vasoocclusion, and expand our knowledge of endothelial cell biology. They may provide the basis for future therapeutic interventions.