TY - JOUR
T1 - Activation of endothelial nitric oxide synthase is critical for erythropoietin-induced mobilization of progenitor cells
AU - Santhanam, Anantha Vijay R.
AU - d'Uscio, Livius V.
AU - Peterson, Timothy E.
AU - Katusic, Zvonimir S.
N1 - Funding Information:
This work was supported in part by National Heart, Lung, and Blood Institute Grant HL-53524 (ZSK), the American Heart Association (AHA) Scientist Development Grant (LVD), AHA Postdoctoral fellowship (AVRS), Roche Foundation for Anemia Research and the Mayo Foundation.
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.peptides.2008.03.016
DO - 10.1016/j.peptides.2008.03.016
M3 - Article
C2 - 18448202
AN - SCOPUS:47649106855
SN - 0196-9781
VL - 29
SP - 1451
EP - 1455
JO - Peptides
JF - Peptides
IS - 8
ER -