ERYTHROPHAGOCYTOSIS INCREASES THE EXPRESSION OF ERYTHROID POTENTIATING ACTIVITY MESSENGER-RNA IN HUMAN MONOCYTE-MACROPHAGES

The aim of the present study was to evaluate whether the erythropoieti c response to hemolysis can be mediated by other regulatory peptides i n addition to erythropoietin. For this purpose, we have investigated t he influence of erythrophagocytosis by human monocytes and macrophages on the mRNA expression of several growth factor genes, including inte rleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM -CSF) and erythroid potentiating activity (EPA), which are supposed to influence erythropoiesis. Immunologically mediated erythrophagocytosi s increased the expression of EPA mRNA (2 to 3 times). Such increase a ppeared to be specifically associated with phagocytosis of erythrocyte s, since phagocytosis of yeast microorganisms or antibody-coated latex particles had no effect on EPA gene expression. Yeast, however, power fully stimulated the expression of GM-CSF, granulocyte colony-stimulat ing factor (G-CSF) and interleukin-6 (IL-6) mRNAs which, with the exce ption of G-CSF, were not influenced by erythrophagocytosis. Erythropoi etin and IL-3 mRNAs were never detected in cultured monocytes, either in control or in treated samples. Our findings may suggest that phagoc ytosis of erythrocytes by monocytes/macrophages increases the expressi on, 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.