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Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin.

ABSTRACT: Erythroblasts adhere to central macrophages forming erythroblastic islands in hematopoietic tissues, but the function of these islands is not understood. Murine erythroblastic islands were reconstituted in vitro with macrophages and developmentally synchronous proerythroblasts. Erythroblasts cocultured with macrophages proliferated 3-fold greater than erythroblasts cultured alone. Direct contact with the macrophages was necessary for this enhanced erythroblast proliferation, which resulted from decreased transit time in the G(0)/G(1) phase of cell cycle. Increased erythroblast proliferation in erythroblastic islands occurred over a wide range of erythropoietin concentrations and was the result of a mechanism different from the antiapoptotic effect of erythropoietin. Erythroblasts adherent to macrophages had slightly delayed enucleation, but otherwise differentiation was similar to erythroblasts cultured alone or those that became nonadherent in cocultures. These results suggest a mechanism for the development of anemias associated with abnormal macrophage function and for reduced responsiveness of those anemias to erythropoietin therapy.

SUBMITTER: Rhodes MM

PROVIDER: S-EPMC2214751 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin.

Rhodes Melissa M MM Kopsombut Prapaporn P Bondurant Maurice C MC Price James O JO Koury Mark J MJ

Blood 20071109 3

Erythroblasts adhere to central macrophages forming erythroblastic islands in hematopoietic tissues, but the function of these islands is not understood. Murine erythroblastic islands were reconstituted in vitro with macrophages and developmentally synchronous proerythroblasts. Erythroblasts cocultured with macrophages proliferated 3-fold greater than erythroblasts cultured alone. Direct contact with the macrophages was necessary for this enhanced erythroblast proliferation, which resulted from ...[more]

PMID: 17993612

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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

Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin.

Publications

Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin.

Similar Datasets

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