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Reprint of: Heme oxygenase 1 affects granulopoiesis in mice through control of myelocyte proliferation.
- Source :
-
Immunobiology [Immunobiology] 2017 Jun; Vol. 222 (6), pp. 846-857. Date of Electronic Publication: 2017 May 31. - Publication Year :
- 2017
-
Abstract
- Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe <superscript>2+</superscript> . We showed that HO-1 knock-out mice (HO-1 <superscript>-/-</superscript> ) have a twofold higher level of granulocytes than wild type (WT) mice, despite decreased concentration of granulocyte colony-stimulating factor (G-CSF) in the blood and reduced surface expression of G-CSF receptor on the hematopoietic precursors. This suggests the effect of HO-1 on granulopoiesis. Here we aimed to determine the stage of granulopoiesis regulated by HO-1. The earliest stages of hematopoiesis were not biased toward myeloid differentiation in HO-1 <superscript>-/-</superscript> mice. Within committed granulocytic compartment, in WT mice, HO-1 was up-regulated starting from myelocyte stage. This was concomitant with up-regulation of miR-155, which targets Bach1, the HO-1 repressor. In HO-1 <superscript>-/-</superscript> mice granulopoiesis was accelerated between myelocyte and metamyelocyte stage. There was a higher fraction of proliferating myelocytes, with increased nuclear expression of pro-proliferative C/EBPβ (CCAAT/enhancer binding protein beta) protein, especially its active LAP (liver-enriched activator proteins) isoform. Also our mathematical model confirmed shortening the myelocyte cyclic-time and prolonged mitotic expansion in absence of HO-1. It seems that changes in C/EBPβ expression and activity in HO-1 <superscript>-/-</superscript> myelocytes can be associated with reduced level of its direct repressor miR-155 or with decreased concentration of CO, known to reduce nuclear translocation of C/EBPs. Mature HO-1 <superscript>-/-</superscript> granulocytes were functionally competent as determined by oxidative burst capacity. In conclusion, HO-1 influences granulopoiesis through regulation of myelocyte proliferation. It is accompanied by changes in expression of transcriptionally active C/EBPβ protein. As HO-1 expression vary in human and is up-regulated in response to chemotherapy, it can potentially influence chemotherapy-induced neutropenia.<br /> (Copyright © 2017. Published by Elsevier GmbH.)
- Subjects :
- Animals
Basic-Leucine Zipper Transcription Factors genetics
Cell Differentiation
Cell Proliferation
Cells, Cultured
Granulocyte Colony-Stimulating Factor metabolism
Hematopoiesis
Heme Oxygenase-1 genetics
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs genetics
Respiratory Burst
Granulocyte Precursor Cells physiology
Granulocytes physiology
Heme Oxygenase-1 metabolism
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3279
- Volume :
- 222
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Immunobiology
- Publication Type :
- Academic Journal
- Accession number :
- 28576353
- Full Text :
- https://doi.org/10.1016/j.imbio.2017.05.006