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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1700-1708.
Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-06-098178.


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RED CELLS

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

Melissa M. Rhodes1, Prapaporn Kopsombut2, Maurice C. Bondurant2, James O. Price3, and Mark J. Koury4

Departments of1 Pediatrics and 2 Medicine, Vanderbilt University Medical Center, Nashville, TN; and the Departments of3 Pathology and 4 Medicine, Veterans Administration Tennessee Valley Healthcare System and Vanderbilt University Medical Center, Nashville, TN

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 G0/G1 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.


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