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

Mateusz Adamiak; Ahmed Abdelbaset-Ismail; Joseph B. Moore; J. Zhao; Ahmed Abdel-Latif; Marcin Wysoczynski; Mariusz Z. Ratajczak

doi:10.1007/s12015-016-9693-1

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

Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Joseph B. Moore, J. Zhao, Ahmed Abdel-Latif, Marcin Wysoczynski, Mariusz Z. Ratajczak

Internal Medicine

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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.

Original language	English
Pages (from-to)	92-103
Number of pages	12
Journal	Stem Cell Reviews and Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1007/s12015-016-9693-1
State	Published - Feb 1 2017

Bibliographical note

Funding Information:
This work was supported by NIH grants 2R01 DK074720 and R01HL112788, the Stella and Henry Endowment, and the Harmonia NCN grant UMO-2014/14/M/NZ3/00475 to MZR. AAI was on leave of absence from the Faculty of Veterinary Medicine, Zagazig University, Egypt.

Publisher Copyright:
© 2016, The Author(s).

Keywords

Complement cascade
HO-1
NO
Stem cell homing
Stem cell mobilization
iNOS

ASJC Scopus subject areas

Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s12015-016-9693-1

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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.",

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author = "Mateusz Adamiak and Ahmed Abdelbaset-Ismail and Moore, {Joseph B.} and J. Zhao and Ahmed Abdel-Latif and Marcin Wysoczynski and Ratajczak, {Mariusz Z.}",

note = "Funding Information: This work was supported by NIH grants 2R01 DK074720 and R01HL112788, the Stella and Henry Endowment, and the Harmonia NCN grant UMO-2014/14/M/NZ3/00475 to MZR. AAI was on leave of absence from the Faculty of Veterinary Medicine, Zagazig University, Egypt. Publisher Copyright: {\textcopyright} 2016, The Author(s).",

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AU - Abdel-Latif, Ahmed

AU - Wysoczynski, Marcin

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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