Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) aktiviert β1-Integrin via CD63 und fördert Migration und Adhäsion hämatopoietischer Stamm- und Progenitorzellen

Homing and engraftment of hematopoietic stem and progenitor cells (HSPCs) during bone marrow transplantation are critically dependent on integrins such as b1-integrin. In the present study, we show that b1-integrin and the tetraspanin CD63 form a cell surface receptor complex for the soluble serum protein tissue inhibitor of metalloproteinases-1 (TIMP-1) on human CD34+ HSPCs. Through binding to this receptor complex, TIMP-1 activates b1-integrin, increases adhesion and migration of human CD34+ cells, and protects these cells from induced apoptosis. TIMP-1 stimulation in murine bone marrow mononuclear cells also promotes migration and adhesion; this is associated with augmented homing of murine mononuclear cells and of murine LSK+ cells during bone marrow transplantation. These results not only indicate that TIMP-1 is conducive to HSPC homing; they also identify CD63 and b1- integrin as a TIMP-1 receptor complex on HSPCs.