Nitric oxide is a regulator of hematopoietic stem cell activity.
Hematopoietic stem cells give rise to various multipotent progenitor populations, which expand in response to cytokines and which ultimately generate all of the elements of the blood. Here we show that it is possible to increase the number of stem and progenitor cells in the bone marrow (BM) by suppressing the activity of NO synthases (NOS). Exposure of mice to NOS inhibitors, either directly or after irradiation and BM transplantation, increases the number of stem cells in the BM. In the transplantation model, this increase is followed by a transient increase in the number of neutrophils in the peripheral blood. Thus, our results indicate that NO is important for the control of hematopoietic stem cells in the BM. They further suggest that suppression of NO synthase activity may allow expansion of the number of hematopoietic stem and progenitor cells or neutrophils for therapeutic purposes.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Tatyana
T
Michurina
Peter
P
Krasnov
Alejandro
A
Balazs
Naoki
N
Nakaya
Tamara
T
Vasilieva
Boris
B
Kuzin
Nikolay
N
Khrushchov
Richard C
RC
Mulligan
Grigori
G
Enikolopov
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000502:physiology*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester