Activation of endothelial nitric oxide synthase is critical for erythropoietin-induced mobilization of progenitor cells

The present study aimed to define the ability of erythropoietin (EPO) to mobilize hematopoietic stem cells (c-kit+/sca-1+/lin-1−; KSL-cells) and hematopoietic progenitor cells (CD34+ cells), including vascular endothelial growth factor receptor 2 expressing hematopoietic progenitor cells (CD34+/Flk-1+ cells). We also sought to determine the role of endothelial nitric oxide synthase (eNOS) in EPO-induced mobilization. Wild type (WT) and eNOS−/− mice were injected bi-weekly with recombinant erythropoietin (EPO, 1000 U/kg, s.c.) for 14 days. EPO increased the number of KSL, CD34+, CD34+/Flk-1+ cells in circulating blood of wild type mice. These effects of EPO were abolished in eNOS−/− mice. Our results demonstrate that, EPO stimulates mobilization of hematopoietic stem and progenitor cells. This effect of EPO is critically dependent on activation of eNOS.