Nitric oxide differentially regulates proliferation and mobilization of endothelial progenitor cells but not of hematopoietic stem cells.
To investigate the role of nitric oxide in controlling endothelial progenitor (EPC) and hematopoietic stem cell (HSC) mobilization, wild-type mice, L-NAME treated WT and eNOS-/- mice received either PBS or G-CSF for 5 days. Under unstimulated conditions bone marrow of either L-NAME treated WT and eNOS-/- mice, representing acute and chronic NO-deficiency, showed higher CD34(+)Flk-I+ EPC numbers compared to their WT littermates. Furthermore, CD34(+)Flk-I+ progenitors under NO-deficient conditions showed a higher cell turn over since the proliferation and apoptosis activity under in vivo as well as in vitro conditions were enhanced. In line with this finding bone marrow derived EPC differentiation towards endothelial cells was modulated in an NO-dependent manner. Administration of G-CSF resulted in an increase of EPC within the bone marrow of WT animals with a consecutive release of these cells into the peripheral circulation. Under NO-deficient conditions G-CSF failed to increase EPC numbers. In contrast, the HSC population c-kit(+)Lin- was not influenced by nitric oxide. Thus, NO differentially supports the mobilization of the endothelial committed progenitor subpopulation in bone marrow but does not have an effect on HSC in vivo.
Ozüyaman
Burcin
B
Universitätsklinik Düsseldorf, Medizinische Klinik und Poliklinik B, Klinik für Kardiologie, Pneumologie und Angiologie, Düsseldorf.
Ebner
Petra
P
Niesler
Ulrike
U
Ziemann
Jutta
J
Kleinbongard
Petra
P
Jax
Thomas
T
Gödecke
Axel
A
Kelm
Malte
M
Kalka
Christoph
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D004791:Enzyme Inhibitors; D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester