Krasnov Peter, Michurina Tatyana, Packer Michael A, Stasiv Yuri, Nakaya Naoki, Moore Kateri A, Drazan Kenneth E, Enikolopov Grigori
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Mol Med. 2008 Mar-Apr;14(3-4):141-9. doi: 10.2119/2007-00011.Krasnov.
Nitric oxide (NO) signaling is important for the regulation of hematopoiesis. However, the role of individual NO synthase (NOS) isoforms is unclear. Our results indicate that the neuronal NOS isoform (nNOS) regulates hematopoiesis in vitro and in vivo. nNOS is expressed in adult bone marrow and fetal liver and is enriched in stromal cells. There is a strong correlation between expression of nNOS in a panel of stromal cell lines established from bone marrow and fetal liver and the ability of these cell lines to support hematopoietic stem cells; furthermore, NO donor can further increase this ability. The number of colonies generated in vitro from the bone marrow and spleen of nNOS-null mutants is increased relative to wild-type or inducible- or endothelial NOS knockout mice. These results describe a new role for nNOS beyond its action in the brain and muscle and suggest a model where nNOS, expressed in stromal cells, produces NO which acts as a paracrine regulator of hematopoietic stem cells.
一氧化氮（NO）信号传导对于造血作用的调节至关重要。然而，单个一氧化氮合酶（NOS）亚型的作用尚不清楚。我们的结果表明，神经元型NOS亚型（nNOS）在体外和体内均调节造血作用。nNOS在成年骨髓和胎儿肝脏中表达，并在基质细胞中富集。从骨髓和胎儿肝脏建立的一组基质细胞系中nNOS的表达与这些细胞系支持造血干细胞的能力之间存在很强的相关性；此外，NO供体可进一步增强这种能力。相对于野生型、诱导型或内皮型NOS基因敲除小鼠，nNOS基因敲除突变体的骨髓和脾脏在体外产生的集落数量增加。这些结果描述了nNOS在大脑和肌肉中的作用之外的新作用，并提出了一个模型，即基质细胞中表达的nNOS产生NO，其作为造血干细胞的旁分泌调节因子发挥作用。
