ACTIVATED ENDOTHELIAL ADHESIVITY IN SC VASOOCCLUSION

描述：(改编自调查人员摘要)本提案的重点是 内皮细胞对与镰刀相关的激动剂的黏附反应 细胞疾病。具体目的是检验以下假设：1) 凝血酶和低氧(I/R)增强内皮细胞对SS-Rb黏附；2)特异性内皮细胞 粘性分子导致粘附性增加；以及3)可识别的 粘附性增加的原因是细胞机制。目标1和目标2将是 在体外进行了研究，并使用镰状细胞病的小鼠模型进行了体内研究。这个 单一关注激活的内皮细胞粘附性提供了一种创新 对这项提议的看法。转基因基因敲除镰刀的可用性 小鼠细胞模型与人类疾病高度一致 最先进的活体显微镜系统提供了卓越的 有机会在体内验证体外黏附现象的重要性。 这些实验有望增强我们对分子的理解。 镰刀状红细胞-内皮细胞黏附机制的研究 镰状细胞血管闭塞的病理生理机制，并扩大我们对 内皮细胞生物学。它们可能会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.