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Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.

ABSTRACT: The erythroblastic island (EI), formed by a central macrophage and developing erythroblasts (EBs), was first described decades ago and was recently shown to play an in vivo role in homeostatic and pathological erythropoiesis. The exact molecular mechanisms, however, mediating the interactions between macrophages and EBs remain unclear. Macrophage-EB attacher (Maea) has previously been suggested to mediate homophilic adhesion bounds bridging macrophages and EBs. Maea-deficient mice die perinatally with anemia and defective erythrocyte enucleation, suggesting a critical role in fetal erythropoiesis. Here, we generated conditional knockout mouse models of Maea to assess its cellular and postnatal contributions. Deletion of Maea in macrophages using Csf1r-Cre or CD169-Cre caused severe reductions of bone marrow (BM) macrophages, EBs, and in vivo island formation, whereas its deletion in the erythroid lineage using Epor-Cre had no such phenotype, suggesting a dominant role of Maea in the macrophage for BM erythropoiesis. Interestingly, Maea deletion in spleen macrophages did not alter their numbers or functions. Postnatal Maea deletion using Mx1-Cre or function inhibition using a novel monoclonal antibody also impaired BM erythropoiesis. These results indicate that Maea contributes to adult BM erythropoiesis by regulating the maintenance of macrophages and their interaction with EBs via an as-yet-unidentified EB receptor.

SUBMITTER: Wei Q

PROVIDER: S-EPMC6418477 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.

Wei Qiaozhi Q Boulais Philip E PE Zhang Dachuan D Pinho Sandra S Tanaka Masato M Frenette Paul S PS

Blood 20190123 11

The erythroblastic island (EI), formed by a central macrophage and developing erythroblasts (EBs), was first described decades ago and was recently shown to play an in vivo role in homeostatic and pathological erythropoiesis. The exact molecular mechanisms, however, mediating the interactions between macrophages and EBs remain unclear. Macrophage-EB attacher (Maea) has previously been suggested to mediate homophilic adhesion bounds bridging macrophages and EBs. <i>Maea</i>-deficient mice die per ...[more]

PMID: 30674470

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Project description:BackgroundTrauma is associated with widespread inflammation, neuroendocrine activation, and an inadequate bone marrow response to anemia. During late-stage erythropoiesis, erythroid progenitors/erythroblasts form clusters on the surface of specialized bone marrow macrophages where they are supported through terminal differentiation and enucleation. We hypothesized that these erythroblastic islands (EBIs) are adversely impacted by severe trauma.MethodsMale Sprague-Dawley rats (n = 8/group) were subjected to either multiple injuries (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus 2 hours of daily chronic restraint stress (PT/CS), or naive controls. Bone marrow was harvested on days 2 and 7. Nuclear-stained, enriched bone marrow EBIs were fixed and stained for CD71, VCAM-1, and CD163, and confocal images were obtained at 20 times magnification. Numbers of erythroid cells/EBI and ratio of reticulocytes/EBI were counted by a blinded observer. Differences were compared using analysis of variance, with significance defined as p < 0.05.ResultsPT and PT/CS had significantly reduced numbers of erythroid cells per EBI on day 2 when compared with naive (PT: 5.9 ± 1.0 cells [ p < 0.05], PT/CS: 6.8 ± 0.8 cells [ p < 0.05] vs. naive: 8.5 ± 0.8 cells). On day 7, the number of erythroid cells/EBI increased following PT (8.3 ± 0.4 cells) but remained reduced following PT/CS (5.9 ± 0.5 cells [ p < 0.05]). This correlated with an increased proportion of reticulocytes/EBI on day 7 following PT, which was not present following PT/CS (PT: 54% [ p < 0.05] vs. PT/CS: 28%).ConclusionLate-stage erythropoiesis was altered following multicompartmental PT early after injury, and these alterations persisted with the addition of daily chronic stress. Alterations in EBI structure and function after severe trauma and critical illness may serve as a promising new area of study to improve mechanistic understanding of persistent anemia after trauma.

Dataset Information

Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.

Publications

Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.

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