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, 1000U/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.
Santhanam
Anantha Vijay R
AV
Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
d'Uscio
Livius V
LV
Peterson
Timothy E
TE
Katusic
Zvonimir S
ZS
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D004921:Erythropoietin / Q000502:physiology*; D019650:Hematopoietic Stem Cell Mobilization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*
D004921:Erythropoietin; D052250:Nitric Oxide Synthase Type III