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Release of erythropoietin from macrophages mediated by phagocytosis of crystalline silica.

The hormone erythropoietin (Ep), which regulates erythropoiesis, can be shown to be released extrarenally from macrophages of the spleen, bone marrow, peritoneal exudate, lung, liver, and fetal liver when suspensions of these cells are preincubated with crystalline silica. The cell supernatants are assayed for Ep activity in the erythroid colony-forming technique using 12- 13-day fresh or cryopreserved fetal liver cell suspensions as a source of Ep-sensitive CFU-E target cells. This report describes the optimal conditions required for release of Ep from silica-treated spleen macrophages. The requirement for phagocytosis of silica in mediating Ep release is shown by four different methods, namely, temperature dependency, inhibition of phagocytosis by Cytochalasin B, the presence of calcium in the medium, and the fact that silica particles coated with serum or poly-2-vinylpyridine-N-oxide can decrease Ep release to control levels. In addition, the reduction to background Ep levels when reduced glutathione, alpha tocopherol (vitamin E), and alpha-thioglycerol are added either separately or in combination with silica-treated macrophages is discussed in terms of a possible mechanism of silica action.