P90	VEGF-induced rapid mobilization of c-kit/sca-1 positive murine bone marrow cells is impaired in urokinase (uPA)- and in urokinase receptor (uPAR)- deficient mice.
M.Dehghani, D.Olcaydu, J.Zaujec, P.Uhrin, B.Binder, J.Breuss
Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, AT.

Thrombolytic events lead by their very nature to local hypoxia and thus via HIF-1α to expression and release of VEGF to counteract the problem of insufficient blood supply by inducing the growth of new blood vessels. In addition VEGF has been shown to induce mobilization of bone marrow stem cells. This process presumably contributes to angiogenesis by delivery of endothelial precursor cells. The process of precursor cell mobilization has been shown to depend on proteolysis. We here wanted to establish the contribution of the uPA/uPAR/plasminogen system to the process of VEGF-induced progenitor cell mobilization. Our approach was to investigate the mobilization of c-kit/sca-1 positive cells to peripheral blood 24 hours after intraperitoneal injection of 50 ng of VEGF165. We assessed the percentage of target cells before and 24 hours after injection by FACS analysis of 30 ul of blood. In wild type animals the increase in the percentage of c-kit/sca-1 positive cells after VEGF165 was 83% while in, uPA and uPAR deficient mice the increase was significantly lower, 21% and 15% respectively. From these date we conclude that urokinase as well as its receptor participate in bone marrow stem cell mobilization in response to VEGF165.

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