title: Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro.
abstract: 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.
authors.affiliation: Medizinische Klinik III, Eberhard Karls Universität Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.forename: Andreas Eberhard
authors.initials: AE
authors.lastname: May
authors.forename: Karin
authors.initials: K
authors.lastname: Daub
authors.forename: Ulrich
authors.initials: U
authors.lastname: Heinzmann
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Iris
authors.initials: I
authors.lastname: Pfisterer
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D017252:CD3 Complex / Q000032:analysis; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D004622:Embryo, Mammalian / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D010973:Platelet Adhesiveness; D013234:Stem Cells / Q000166:cytology*
chemical_list: D017252:CD3 Complex