Differential chemokine receptor expression regulates functional specialization of endothelial progenitor cell subpopulations

Abstract

Postnatal vasculogenesis is mediated by endothelial progenitor cells (EPCs) which consist of subpopulations with different functional capacities. Our goal was to profile chemokine receptor expression on relevant subsets of EPCs and to characterize their role for effector functions. CD34(+)/CD133(+)/VEGFR2(+) EPCs were characterized by high expression of chemokine receptors CXCR4, CX3CR1, BLT1, and low level expression of CXCR2 and CCR2, while primordial CD34(-)/CD133(+)/VEGFR2(+) EPCs express these chemokine receptors at comparably low levels. Migration assays revealed that SDF-1, fractalkine, and LTB4 significantly increase migration of CD34(-)/CD133(+)/VEGFR2(+) EPCs, while SDF-1 was the only potent agonist of migration of CD34(+)/CD133(+)/VEGFR2(+) EPCs. SDF-1, fractalkine, and LTB4 trigger significant increase adhesion of CD34(+)/CD133(+)/VEGFR2(+) EPCs, while in CD34(-)/CD133(+)/VEGFR2(+) EPCs SDF-1 and fractalkine are equipotent agonists and LTB4 triggers a smaller though still significant increase in adhesion. Differential expression of specific chemokine receptors is an important regulator in terms of migration and adhesion of biologically relevant EPC-subpopulations, which may have implications for cell therapeutic strategies for treatment of ischemic vascular disease.