Journal article
Nrf2 deficiency in mice attenuates erythropoietic stress-related macrophage hypercellularity
Experimental hematology, Vol.84, pp.19-28.e4
04/01/2020
DOI: 10.1016/j.exphem.2020.02.005
PMCID: PMC7237317
PMID: 32151553
Abstract
Erythropoiesis in the bone marrow and spleen depends on intricate interactions between the resident macrophages and erythroblasts. Our study focuses on identifying the role of nuclear factor erythroid 2-related factor 2 (Nrf2) during recovery from stress erythropoiesis. To that end, we induced stress erythropoiesis in Nrf2(+/+) and Nrf2-null mice and evaluated macrophage subsets known to support erythropoiesis and erythroid cell populations. Our results confirm macrophage and erythroid hypercellularity after acute blood loss. Importantly, Nrf2 depletion results in a marked numerical reduction of F4/80(+)/CD169(+)/CD11b(+) macrophages, which is more prominent under the induction of stress erythropoiesis. The observed macrophage deficiency is concomitant to a significantly impaired erythroid response to acute stress erythropoiesis in both murine bone marrow and murine spleen. Additionally, peripheral blood reticulocyte count as a response to acute blood loss is delayed in Nrf2-deficient mice compared with age-matched controls (11.0 +/- 0.6% vs. 14.8 +/- 0.6%, p <= 0.001). Interestingly, we observe macrophage hypercellularity in conjunction with erythroid hyperplasia in the bone marrow during stress erythropoiesis in Nrf2(+/+) controls, with both impaired in Nrf2(-/-)mice. We further confirm the finding of macrophage hypercellularity in another model of erythroid hyperplasia, the transgenic sickle cell mouse, characterized by hemolytic anemia and chronic stress erythropoiesis. Our results revealed the role of Nrf2 in stress erythropoiesis in the bone marrow and that macrophage hypercellularity occurs concurrently with erythroid expansion during stress erythropoiesis. Macrophage hypercellularity is a previously underappreciated feature of stress erythropoiesis in sickle cell disease and recovery from blood loss. (C) 2020 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Nrf2 deficiency in mice attenuates erythropoietic stress-related macrophage hypercellularity
- Creators
- Oluwabukola T. Gbotosho - University of PittsburghMaria G. Kapetanaki - University of PittsburghMark Ross - University of PittsburghSamit Ghosh - University of PittsburghFrances Weidert - University of PittsburghGrant C. Bullock - University of PittsburghSimon Watkins - University of PittsburghSolomon F. Ofori-Acquah - University of PittsburghGregory J. Kato - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Experimental hematology, Vol.84, pp.19-28.e4
- DOI
- 10.1016/j.exphem.2020.02.005
- PMID
- 32151553
- PMCID
- PMC7237317
- NLM abbreviation
- Exp Hematol
- ISSN
- 0301-472X
- eISSN
- 1873-2399
- Publisher
- Elsevier
- Number of pages
- 14
- Grant note
- Institute for Transfusion Medicine Hemostasis at the University of Pittsburgh School of Medicine HL133864; MD009162 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Pittsburgh Department of Pathology R01HL106192; U01HL117721; U54HL141011 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Vascular Biology Research Institute at the University of Pittsburgh School of Medicine
- Language
- English
- Date published
- 04/01/2020
- Academic Unit
- Pathology
- Record Identifier
- 9984697737802771
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