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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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Submitted June 27, 2007
Accepted October 31, 2007

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

Melissa M Rhodes, Prapaporn Kopsombut, Maurice C Bondurant, James O Price, and Mark J Koury*

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
Department of Pathology, VA Tennessee Valley Healthcare System & Vanderbilt University Medical Center, Nashville, TN, United States
Department of Medicine, VA Tennessee Valley Healthcare System & Vanderbilt University Medical Center, Nashville, TN, United States

* Corresponding author; email: mark.koury{at}vanderbilt.edu.

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 co-cultured with macrophages proliferated three-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 due to a different mechanism than the anti-apoptotic 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 co-cultures. 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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