Inducible Nitric Oxide Synthase (iNOS) Is a Novel Negative Regulator of Hematopoietic Stem/Progenitor Cell Trafficking

被引：42

作者：

Adamiak, Mateusz ^{[1
,4
]}

Abdelbaset-Ismail, Ahmed ^{[1
]}

Moore, Joseph B. ^{[2
]}

Zhao, J. ^{[2
]}

Abdel-Latif, Ahmed ^{[3
]}

Wysoczynski, Marcin ^{[2
]}

Ratajczak, Mariusz Z. ^{[1
,4
]}

机构：

[1] Univ Louisville, Stem Cell Inst, James Graham Brown Canc Ctr, 500 S Floyd St Rm 107, Louisville, KY 40202 USA

[2] Univ Louisville, Inst Mol Cardiol, Louisville, KY 40292 USA

[3] Univ Kentucky, Gill Heart Inst, Div Cardiovasc Med, Lexington, KY USA

[4] Med Univ Warsaw, Dept Regenerat Med, Warsaw, Poland

来源：

STEM CELL REVIEWS AND REPORTS | 2017年 / 13卷 / 01期

关键词：

iNOS; NO; Stem cell mobilization; Stem cell homing; Complement cascade; HO-1; BONE-MARROW; STEM-CELLS; COMPLEMENT CASCADE; HEME OXYGENASE-1; PROGENITOR CELLS; INNATE IMMUNITY; MOBILIZATION; EXPRESSION; ACTIVATION; NEUTROPHILS;

D O I：

10.1007/s12015-016-9693-1

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Nitric oxide (NO) is a gaseous free radical molecule involved in several biological processes related to inflammation, tissue damage, and infections. Based on reports that NO inhibits migration of granulocytes and monocytes, we became interested in the role of inducible NO synthetase (iNOS) in pharmacological mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). To address the role of NO in HSPC trafficking, we upregulated or downregulated iNOS expression in hematopoietic cell lines. Next, we performed mobilization studies in iNOS(-/-)mice and evaluated engraftment of iNOS(-/-)HSPCs in wild type (control) animals. Our results indicate that iNOS is a novel negative regulator of hematopoietic cell migration and prevents egress of HSPCs into PB during mobilization. At the molecular level, downregulation of iNOS resulted in downregulation of heme oxygenase 1 (HO-1), and, conversely, upregulation of iNOS enhanced HO-1 activity. Since HO-1 is a negative regulator of cell migration, the inhibitory effects of iNOS identified by us can be at least partially explained by its enhancing the HO-1 level in BM cells.

引用

页码：92 / 103

页数：12

共 47 条

[1]

Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1 [J].