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Mechanism of Macrophage Reversal of Friend Erythroleukemia: Macrophage Regulation of Normal and Leukemic Erythropoiesis¹

Department of Cell Biology, AMC Cancer Research Center, Denver, Colorado 80214

The acute erythroleukemia induced in mice by the anemia-inducing strain of the Friend virus complex is caused to regress by normal macrophages. We examined the possibility that reversal of leukemia is related to a macrophage regulatory function in erythropoiesis. We found that the ability of macrophages to induce leukemia regression correlates with nonimmunological, in vivo suppression of normal and susceptible leukemic erythroid progenitors. The macrophage effect on erythropoiesis appears to be due to changes in a humoral regulator, related to but independent of erythropoietin. The results suggest a novel regulatory system for erythropoiesis, operative in vivo, and involving macrophages as accessory or suppressor cells. This regulation appears to be disrupted in erythroleukemic mice, but can be restored, and the disease can be made to regress by treatment with normal macrophages.

¹ Supported in part by USPHS Grant CA33188 and gifts to the AMC Cancer Research Center from Don Strauss and the Gannett Foundation.

² To whom requests for reprints should be addressed, at Department of Cell Biology, AMC Cancer Research Center, 1600 Pierce Street, Denver, CO 80214.

³ Recipient of a special Fellow Award from the Leukemia Society of America, Inc. Present address: Medical Biology Institute, LaJolla, CA 92037.

Received 1/ 7/86. Revised 3/31/86. Accepted 5/ 1/86.