title: Inducible Nitric Oxide Synthase (iNOS) Is a Novel Negative Regulator of Hematopoietic Stem/Progenitor Cell Trafficking.
abstract: 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.
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street Rm. 107, Louisville, KY, 40202, USA.|Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Adamiak
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street Rm. 107, Louisville, KY, 40202, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdelbaset-Ismail
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Moore
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Latif
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wysoczynski
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street Rm. 107, Louisville, KY, 40202, USA. mzrata01@louisville.edu.|Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland. mzrata01@louisville.edu.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1
keywords: Complement cascade; HO-1; NO; Stem cell homing; Stem cell mobilization; iNOS