CD43 AND REGULATION OF BLOOD CELL ADHESION

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In clinical practice over the past two decades, there has been a striking increase in the use of blood cell products and correspondingly, a heightened interest in improving the means by which to maintain their functional integrity and understanding the conditions that might adversely affect their survival. CD43 is a sialoglycoprotein expressed on the surface of virtually all cells of hematopoietic origin and its has been shown to have anti-adhesive properties. We propose that the anti-adhesive effect of CD43 is important in regulating the adhesiveness of circulating blood cells and maintaining the functional integrity of blood cell products. The long-term objective of this project is to identify and characterize the physiologically relevant effects of CD43 on the circulatory dynamics and function of human blood cells. In the first specific aim, we will directly examine the role of CD43 in the regulation of leukocyte trafficking, homing and recruitment using a murine model of CD43 deficiency that we have recently generated by gene targeting. We also will determine the importance of CD43 on the survival of transfused blood cells and investigate its role in progenitor/stem cell function as it applies to the ability of such cells to be mobilized and reconstitute hematopoiesis. In the second specific aim, we will study physiological mechanisms that alter or remove CD43 from blood cell surfaces and determine the impact of CD43 alterations on leukocytes, platelets and hematopoietic progenitor cells. Mechanisms by which CD43 is cleaved and released during leukocyte activation and storage will be examined and the probable functions of a soluble CD43 from present at high levels in blood will be explored. The consequences of CD43 alterations on the functional integrity of donor blood cell products will be determined, and deleterious effects in recipients of cells with altered CD43 will be identified.