Interactions Between Sickle Cells and Adherent Platelets

描述(申请人提供)本研究将主要在尼日利亚进行，作为美国国立卫生研究院#R01 HL54462号拨款的延伸。本研究将探讨激动剂诱导的纤维连接蛋白(FN)基质聚集的机制，以及血小板导向的FN基质在镰状细胞病(SCD)发病机制中的可能作用。凝血系统的激活，特别是血小板的激活，与SCD的血管闭塞事件有关。我们最近证明，贴壁的血小板可以被诱导组装成FN的基质。我们将更全面地研究这种组装的机制，重点是整合素的作用。然后，我们将研究在成纤维细胞的情况下，血栓反应蛋白-1(TSP-1)是否沉积在血小板的FN基质中。我们将了解SCD患者的血小板是否有能力沉积FN和TSP的基质。最后，我们将研究SCD患者的网织红细胞和红细胞是否具有FN和TSP-1的细胞表面受体，是否特异性地附着在黏附的血小板的基质上。这些研究可能揭示了镰状细胞黏附的一个重要机制，这是药物操纵的结果。

DESCRIPTION (provided by applicant)This research will be done primarily in Nigeria as an extension of NIH grant #R01 HL54462. This study will examine the mechanisms involved in agonist-induced fibronectin (FN) matrix assembly by platelets adherent on various matrix proteins and the possible relevance of platelet-directed FN matrix to the pathogenesis of sickle cell disease (SCD). Activation of the coagulation system and specifically of platelets has been implicated in the vasooclusive events of SCD. We recently demonstrated that adherent platelets can be induced to assemble a matrix of FN. We will investigate the mechanisms of such assembly more completely, concentrating on the role of integrins. We then will investigate whether, as in the case with fibroblasts, thrombospondin-1 (TSP-1) deposits in the FN matrix of platelets. We will learn whether platelets of patients with SCD have the capacity to deposit a matrix of FN and TSP. Finally, we will investigate whether reticulocytes and red blood cells of patients with SCD, which have cell surface receptors for FN and TSP-1, adhere specifically to the matrix of adherent platelets. These studies may reveal an important mechanism for adherence of sickle cells that is amenable to pharmacological manipulation