Einfluss von löslichem P-Selektin auf Hämostase und Thrombose

• Antragsteller: Dr. Wolfgang Bergmeier
• Fachliche Zuordnung: Pharmakologie
• Förderung: Förderung von 2002 bis 2005
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5393300

Adhesion receptors expressed on the surface of endothelial cells, platelets, and other hematopoietic cells play an essential role in thrombosis and hemostasis. Some of these receptors are detectable in a soluble form in plasma, but their physiologic function(s) are poorly defined. Soluble P-selectin (sP-sel) was recently shown to induce by enhanced fibrin formation and deposition on growing thrombi. This unexpected function leads to speculations regarding an active role for sP-sel in different clinical complications where increased plasma levels of this molecule have been detected. The studies presented here aim to elucidate the molecular mechanisms involved in sP-sel-induced microparticel formation, to study the role of these microparticels in thrombus formation, and to evaluate possible beneficial effects of sP-sel in clinical bleeding complications. Among others, the methodological approaches include (1) novel flow cytometric assays for studies on mouse blood cells, (2) generation of transgenic mice overexpessing sP-sel, (3) in vitro and ex vivo flow chamber experiments, and in vivo intravital microscopic studies on thrombus formation, and finally (4) clinically relevant mouse models for human bleeding complications.

• DFG-Verfahren: Emmy Noether-Auslandsstipendien