Interactions Between Sickle Cells and Adherent Platelets

本研究将主要在尼日利亚进行，作为NIH资助#R01 HL54462的延伸。本研究将探讨激动剂诱导的纤维连接蛋白（FN）基质通过血小板粘附在各种基质蛋白上组装的机制，以及血小板导向的FN基质与镰状细胞病（SCD）发病机制的可能相关性。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。我们最近证明粘附血小板可以被诱导组装FN基质。我们将更全面地研究这种组装的机制，集中在整合素的作用上。然后我们将研究是否，在成纤维细胞的情况下，血小板反应蛋白-1 （TSP-1）沉积在血小板的FN基质中。我们将了解SCD患者的血小板是否具有沉积FN和TSP基质的能力。最后，我们将研究SCD患者的网状红细胞和红细胞是否具有特异性粘附血小板基质，它们具有FN和TSP-1的细胞表面受体。这些研究可能揭示了镰状细胞粘附的重要机制，该机制可通过药理操作

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