Impaired protein synthesis in erythroblasts enhances their phagocytosis by macrophages

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Abstract
To elucidate mechanisms which underly ineffective erythropoiesis, the effect of impaired macromolecular synthesis in erythroblasts on their phagocytosis by macrophages in vitro was investigated. Dimethylsulfoxide-induced murine Friend leukemia erythroblasts were treated with inhibitors of RNA or protein synthesis and subsequently tested for their interaction with syngeneic mouse peritoneal macrophages in culture. Exposure of the erythroblasts to 2 reversible inhibitors of protein synthesis, puromycin and cycloheximade, enhanced their association with and phagocytosis by macrophages. The effect was evident after the drugs had caused a partial inhibition of protein synthesis and appeared to be reversible. The treatment of erythroblasts with the inhibitor of RNA-synthesis, actinomycin D, which caused a marked depression of RNA but not of protein synthesis, failed to affect the interaction of erythroblasts with macrophages. The results are in keeping with previous observations on human bone marrow showing impaired protein synthesis in erythroblasts in some hematological disorders characterized by a marked increase in ineffective erythropoiesis.