CD43 AND REGULATION OF BLOOD CELL ADHESION

在过去二十年的临床实践中， 血细胞制品的使用增加， 提高了对改善维持其 功能完整性和了解可能不利的条件 影响他们的生存。 CD 43是一种表达在细胞表面的唾液酸糖蛋白 几乎所有造血起源细胞的表面， 显示出具有防粘性能。 我们建议， CD 43在调节循环免疫中的作用是重要的， 血细胞和维持血细胞的功能完整性 产品. 该项目的长期目标是确定和 表征CD 43对细胞的生理学相关作用， 循环动力学和人体血细胞的功能。 上 具体目标，我们将直接检查CD 43在调节中的作用， 白细胞运输，归巢和招募使用小鼠模型， 我们最近通过基因靶向产生的CD 43缺陷。 我们 还将确定CD 43对输血后存活的重要性。 血细胞，并研究其在祖细胞/干细胞功能中的作用， 它适用于这些细胞的动员和重组能力， 造血 在第二个具体目标中，我们将研究生理学 从血细胞表面改变或去除CD 43的机制， 确定CD 43改变对白细胞、血小板和 造血祖细胞 CD 43被切割的机制， 将检查在白细胞活化和储存期间释放的 可溶性CD 43在血液中高水平存在的可能功能 将被探索。 CD 43改变对功能性 将确定供体血细胞产物的完整性， 将鉴定具有改变的CD 43的细胞的受体中的作用。

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.