Einfluss von löslichem P-Selektin auf Hämostase und Thrombose

表达于内皮细胞、血小板和其他造血细胞表面的黏附受体在血栓形成和止血中起重要作用。其中一些受体可以在血浆中以可溶形式检测到，但它们的生理功能(S)尚不清楚。近年来发现，可溶性P-选择素(sP-sel)可通过促进血栓上纤维蛋白的形成和沉积而被诱导。这一意想不到的功能导致了人们对sP-sel在不同临床并发症中的积极作用的猜测，在不同的临床并发症中，已检测到该分子水平的升高。这些研究旨在阐明SP-SEL诱导微粒子形成的分子机制，研究这些微粒子在血栓形成中的作用，并评估SP-SEL在临床出血并发症中可能的有益作用。其中，方法学方法包括(1)用于研究小鼠血细胞的新的流式细胞术分析，(2)过量表达的转基因小鼠的产生，(3)体外和体外流室实验，以及体内血栓形成的活体显微镜研究，以及(4)临床上与人类出血并发症相关的小鼠模型。

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.