Summary
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 playa 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/cm2, 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.
Keywords
Platelets - endothelial progenitor cells - interaction