Reprint of: Heme oxygenase 1 affects granulopoiesis in mice through control of myelocyte proliferation
| Autor: | Krzysztof Szade, Maciej Siedlar, Maciej Ciesla, Anna Konturek, Robert Straka, Karolina Bukowska-Strakova, Karolina Najder, Małgorzata Tyszka-Czochara, Alicja Jozkowicz, Witold Nowak, Agata Szade, Jozef Dulak |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Metamyelocyte Immunology Granulocyte Biology Granulopoiesis Mice 03 medical and health sciences Enhancer binding Granulocyte Colony-Stimulating Factor medicine Animals Immunology and Allergy Granulocyte Precursor Cells Cells Cultured Cell Proliferation Respiratory Burst Mice Knockout Membrane Proteins Cell Differentiation Hematology Molecular biology Hematopoiesis Mice Inbred C57BL Heme oxygenase MicroRNAs Haematopoiesis Basic-Leucine Zipper Transcription Factors 030104 developmental biology medicine.anatomical_structure Biochemistry Myelocyte Heme Oxygenase-1 Granulocytes |
| Zdroj: | Immunobiology. 222:846-857 |
| ISSN: | 0171-2985 |
| DOI: | 10.1016/j.imbio.2017.05.006 |
| Popis: | Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe2+. We showed that HO-1 knock-out mice (HO-1-/-) 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-/- 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-/- 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-/- 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-/- 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. |
| Databáze: | OpenAIRE |
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