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Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications

Evidence indicates that bone marrow (BM)-residing hematopoietic stem/progenitor cells (HSPCs) are released into peripheral blood (PB) after administration of pro-mobilizing drugs, which induce a state of sterile inflammation in the BM microenvironment. In the reverse process, as seen after hematopoi...

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Autores principales: Ratajczak, Mariusz Z., Adamiak, Mateusz, Ratajczak, Janina, Kucia, Magda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166705/
https://www.ncbi.nlm.nih.gov/pubmed/33196976
http://dx.doi.org/10.1007/s12015-020-10083-w
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author Ratajczak, Mariusz Z.
Adamiak, Mateusz
Ratajczak, Janina
Kucia, Magda
author_facet Ratajczak, Mariusz Z.
Adamiak, Mateusz
Ratajczak, Janina
Kucia, Magda
author_sort Ratajczak, Mariusz Z.
collection PubMed
description Evidence indicates that bone marrow (BM)-residing hematopoietic stem/progenitor cells (HSPCs) are released into peripheral blood (PB) after administration of pro-mobilizing drugs, which induce a state of sterile inflammation in the BM microenvironment. In the reverse process, as seen after hematopoietic transplantation, intravenously injected HSPCs home and engraft into BM niches. Here again, conditioning for transplantation by myeloablative chemo- or radiotherapy induces a state of sterile inflammation that promotes HSPC seeding to BM stem cell niches. Therefore, the trafficking of HSPCs and their progeny, including granulocytes and monocytes/macrophages, is regulated by a response to pro-inflammatory stimuli. This responsiveness to inflammatory cues is also preserved after malignant transformation of hematopoietic cells. Results from our laboratory indicate that the responsiveness of hematopoietic cells to pro-inflammatory stimuli is orchestrated by Nlrp3 inflammasome. As reported, HO-1 effectively attenuates intracellular activation of Nlrp3 inflammasome as well as the pro-inflammatory effects of several humoral mediators, including complement cascade (ComC) cleavage fragments that promote migration of hematopoietic cells. Based on this finding, inhibition of HO-1 activity may become a practical strategy to enhance the mobilization and homing of normal HSPCs, and, alternatively, its activation may prevent unwanted spread and in vivo expansion of leukemic cells. [Figure: see text]
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spelling pubmed-81667052021-06-03 Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications Ratajczak, Mariusz Z. Adamiak, Mateusz Ratajczak, Janina Kucia, Magda Stem Cell Rev Rep Article Evidence indicates that bone marrow (BM)-residing hematopoietic stem/progenitor cells (HSPCs) are released into peripheral blood (PB) after administration of pro-mobilizing drugs, which induce a state of sterile inflammation in the BM microenvironment. In the reverse process, as seen after hematopoietic transplantation, intravenously injected HSPCs home and engraft into BM niches. Here again, conditioning for transplantation by myeloablative chemo- or radiotherapy induces a state of sterile inflammation that promotes HSPC seeding to BM stem cell niches. Therefore, the trafficking of HSPCs and their progeny, including granulocytes and monocytes/macrophages, is regulated by a response to pro-inflammatory stimuli. This responsiveness to inflammatory cues is also preserved after malignant transformation of hematopoietic cells. Results from our laboratory indicate that the responsiveness of hematopoietic cells to pro-inflammatory stimuli is orchestrated by Nlrp3 inflammasome. As reported, HO-1 effectively attenuates intracellular activation of Nlrp3 inflammasome as well as the pro-inflammatory effects of several humoral mediators, including complement cascade (ComC) cleavage fragments that promote migration of hematopoietic cells. Based on this finding, inhibition of HO-1 activity may become a practical strategy to enhance the mobilization and homing of normal HSPCs, and, alternatively, its activation may prevent unwanted spread and in vivo expansion of leukemic cells. [Figure: see text] Springer US 2020-11-16 2021 /pmc/articles/PMC8166705/ /pubmed/33196976 http://dx.doi.org/10.1007/s12015-020-10083-w Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ratajczak, Mariusz Z.
Adamiak, Mateusz
Ratajczak, Janina
Kucia, Magda
Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications
title Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications
title_full Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications
title_fullStr Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications
title_full_unstemmed Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications
title_short Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications
title_sort heme oxygenase 1 (ho-1) as an inhibitor of trafficking of normal and malignant hematopoietic stem cells – clinical and translational implications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166705/
https://www.ncbi.nlm.nih.gov/pubmed/33196976
http://dx.doi.org/10.1007/s12015-020-10083-w
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