Langer Harald, May Andreas Eberhard, Daub Karin, Heinzmann Ulrich, Lang Peter, Schumm Michael, Vestweber Dietmar, Massberg Steffen, Schönberger Tanja, Pfisterer Iris, Hatzopoulos Antonis K, Gawaz Meinrad
Medizinische Klinik III, Eberhard Karls Universität Tübingen, Germany.
Circ Res. 2006 Feb 3;98(2):e2-10. doi: 10.1161/01.RES.0000201285.87524.9e. Epub 2005 Dec 22.
The homing and differentiation mechanisms of endothelial progenitor cells (EPCs) at sites of vascular lesions are unclear. To investigate whether platelets play a role in the recruitment and differentiation of EPCs, we made use of a robust mouse embryonic EPC (eEPC) line that reliably differentiates to a mature endothelial phenotype. We found that platelets stimulate chemotaxis and migration of these murine eEPCs. Further, the substantial adhesion of murine eEPCs on immobilized platelets that occurs under dynamic flow conditions is inhibited by neutralizing anti-P-selectin glycoprotein ligand-1 and anti-VLA-4 (beta1-integrin) monoclonal antibodies but not by anti-CD11b (aM-integrin; macrophage antigen-1). Coincubation of murine eEPCs with platelets for 5 days induced differentiation of EPCs to mature endothelial cells as verified by positive von Willebrand factor immunofluorescence and detection of Weibel Palade bodies through electron microscopy. We conclude that platelets may play a critical part in the capture and subsequent differentiation of murine eEPCs at sites of vascular lesions, revealing a possible new role of platelets in neoendothelization after vascular injury.
血管损伤部位内皮祖细胞（EPCs）的归巢和分化机制尚不清楚。为了研究血小板是否在EPCs的募集和分化中发挥作用，我们利用了一种强大的小鼠胚胎EPC（eEPC）系，该细胞系能可靠地分化为成熟的内皮表型。我们发现血小板可刺激这些小鼠eEPCs的趋化性和迁移。此外，在动态流动条件下，小鼠eEPCs在固定化血小板上的大量黏附受到抗P-选择素糖蛋白配体-1和抗VLA-4（β1整合素）单克隆抗体的抑制，但不受抗CD11b（αM整合素；巨噬细胞抗原-1）的抑制。小鼠eEPCs与血小板共孵育5天可诱导EPCs分化为成熟内皮细胞，这通过血管性血友病因子免疫荧光阳性和电子显微镜检测Weibel-Palade小体得以证实。我们得出结论，血小板可能在血管损伤部位捕获并随后分化小鼠eEPCs中起关键作用，揭示了血小板在血管损伤后新生内皮化中的一种可能新作用。
