Erythrophagocytosis increases the expression of erythroid potentiating activity mRNA in human monocyte-macrophages.

The aim of the present study was to evaluate whether the erythropoietic response to hemolysis can be mediated by other regulatory peptides in addition to erythropoietin. For this purpose, we have investigated the influence of erythrophagocytosis by human monocytes and macrophages on the mRNA expression of several growth factor genes, including interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF) and erythroid potentiating activity (EPA), which are supposed to influence erythropoiesis. Immunologically mediated erythrophagocytosis increased the expression of EPA mRNA (2 to 3 times). Such increase appeared to be specifically associated with phagocytosis of erythrocytes, since phagocytosis of yeast microorganisms or antibody-coated latex particles had no effect on EPA gene expression. Yeast, however, powerfully stimulated the expression of GM-CSF, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNAs which, with the exception of G-CSF, were not influenced by erythrophagocytosis. Erythropoietin and IL-3 mRNAs were never detected in cultured monocytes, either in control or in treated samples. Our findings may suggest that phagocytosis of erythrocytes by monocytes/macrophages increases the expression, and possibly the production, of EPA. This could in turn potentiate the erythropoietic response to extravascular hemolysis by increasing the number of cells responsive to erythropoietin. Thus, EPA might be a mediator of an end-product positive feedback on the rate of red cell production