Impaired protein synthesis in erythroblasts enhances their phagocytosis by macrophages.

In an attempt to elucidate mechanisms which underly ineffective erythropoiesis, we investigated the effect of impaired macromolecular synthesis in erythroblasts on their phagocytosis by macrophages in vitro. Dimethylsulphoxide-induced murine Friend leukaemia 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 two reversible inhibitors of protein synthesis, puromycin and cycloheximide, 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. By contrast, 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 erythroblats with macrophages. The results are in keeping with previous observations on human bone marrow showing impaired protein synthesis in erythroblasts in some haematological disorders characterized by a marked increase in ineffective erythropoiesis.