title: Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix.
abstract: Endothelial progenitor cells (EPCs) mobilize from the bone marrow in response to tissue injury and participate in vascular repair. However, there is limited data about the homing mechanisms of EPCs to vascular injury sites. Recently animal experiments indicated that platelets play a role in recruitment of EPCs to injury sites. However, data on the possible interaction between platelets and EPCs within the human system are limited. We, therefore, examined in-vitro human platelet-EPC interaction under static and flow conditions. Human EPCs were isolated from donated buffy coats by magnetic microbeads and flow cytometry cell sorting using CD133 and VEGFR-2, respectively, as markers. Platelets were tested in the form of washed platelets, platelet rich plasma or whole blood. EPCs formed heterotypic aggregates with resting platelets under static conditions, an interaction that was greatly enhanced when platelets were activated by collagen, ADP or thrombin-activation peptide. The platelet-EPC interaction was inhibited by antibodies to P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1), but not by antibodies to glycoproteins Ib-IX-V or IIb/IIIa. When perfused over activated platelets under shear stress of 2.5 dyn/cm(2), EPCs tethered to platelayers and either adhered immediately or rolled a short distance before adhering. In addition, platelets promoted the colonization of adherent EPCs in culture conditions. Consistent with recent animal studies, these findings demonstrate that human EPCs interact in vitro with activated platelets under static and flow conditions, mediated through P-selectin-PSGL-1 interaction. This interaction may be a central mechanism for homing of EPCs to vascular injury sites.
authors.affiliation: The Methodist Hospital Research Institute and The Methodist DeBakey Heart Center, Houston, TX, USA.
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Khatira
authors.initials: K
authors.lastname: Aboulfatova
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.forename: Carlos
authors.initials: C
authors.lastname: Alviar
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: Jing-fei
authors.initials: JF
authors.lastname: Dong
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010974:Platelet Aggregation; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*; D013314:Stress, Mechanical; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; C000606023:PROM1 protein, human; D010455:Peptides; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2