Published online before print December 22, 2005, doi: 10.1161/01.RES.0000201285.87524.9e
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Submitted on July 17, 2005
Revised on December 3, 2005
Accepted on December 14, 2005
Adherent Platelets Recruit and Induce Differentiation of Murine Embryonic Endothelial Progenitor Cells to Mature Endothelial Cells In Vitro
Harald Langer ;
From the Medizinische Klinik III (H.L., A.E.M., K.D., T.S., M.G.), Eberhard Karls Universität Tübingen, Germany; GSF-Research Center for Environment and Health (U.H.), Institute of Pathology, Munich; Clinic for Pediatrics (P.L., M.S.), Eberhard Karls Universität Tübingen, Germany; Institute of Cell Biology (D.V.), ZMBE, University of Münster, Germany; Deutsches Herzzentrum München (S.M.), Technische Universität München, Germany; and GSF-Research Center for Environment and Health (I.P., A.K.H.), Institute for Clinical Molecular Biology and Tumor Genetics, Munich, Germany and Vanderbilt University Medical Center, Division of Cardiovascular Medicine, Nashville, Tenn.
* To whom correspondence should be addressed. E-mail: meinrad.gawaz{at}med.uni-tuebingen.de.
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-PSGL-1 and anti-VLA-4 (
1-integrin) monoclonal antibodies but not by anti-CD11b (aM-integrin; MAC-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.
Key words: endothelial progenitor cells • platelets • endothelization • vascular lesion • adhesion
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