The application proposes to elucidate the molecular mechanisms which cause sickle red blood cells to adhere to vascular endothelium. It is clear that this phenomenon may contribute to the clinical problems of sickle vascular crises, and improved understanding of the molecules involved in this process may lead to new therapeutic approaches. The investigators will focus their efforts on the probable role of basal cell adhesion molecule which is also the molecular site of the Lutheran antigens (B-CAM/LU) and the extracellular protein laminin. They will seek to define the molecular epitopes responsible for this association and to establish whether there is ancillary involvement of protein CD44. Similarly, they will seek to define the molecular interactions of integrin associated protein (IAP) with thrombospondin. Finally, they will evaluate the associations of these and other membrane proteins under simulated physiological conditions by measuring the associations of these molecules with extracellular matrix and with disrupted vascular endothelium using a flow chamber model.
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