Effects of actinomycin D in vivo on murine erythroid stem cells

Abstract

Low-dose actinomycin D (Acto) selectively suppresses murine erythropoiesis without decreasing erythropoietin (Ep) production. We used the plasma clot system to determine the stage of erythroid differentiation at which this inhibition occurs. Late erythroid precursors, CFU-E, and less differentiated committed erythroid stem cells, BFU-E, were assayed in CF1 mice given Acto 75–82 microgram/kg/day or saline subcutaneously for 5 days. We also assayed pluripotent (CFU-S) and committed granulocyte-monocyte (CFU-C) stem cells. Reticulocytes and marrow and spleen nucleated erythroid precursors were decreased by 99% in the Acto-treated mice; tibial marrow CFU-E were decreased by 97% and splenic CFU-E by 99%. Tibial BFU- E were not decreased by Acto, although there was a 66% diminution in splenic BFU-E. Acto increased tibial CFU-S, but splenic CFU-S and tibial and splenic CFU-C were unchanged. Thus Acto inhibits erythropoiesis by suppressing the ability of immediate committed erythroid precursors of CFU-E or CFU-E themselves to differentiate further in response to Ep. Acto does not affect survival or proliferation of the less differentiated cells--CFU-C, CFU-S, and marrow BFU-E. The suppression of splenic BFU-E in Acto-treated mice may indicate that marrow and splenic BFU-E are basically different stem cells. Alternatively, Acto treatment may impair migration of BFU-E from marrow to spleen.