Release of erythropoietin from macrophages by treatment with silica.
An erythropoietic stimulating factor (ESF) can be shown to be released from preincubated macrophage-containing cell suspensions from mice by the macrophage-specific, cytotoxic agent, silica. A concentrated silica-treated spleen cell supernatant containing ESF is shown to cause a dose-dependent increase in 59Fe incorporation into red blood cells using the in vivo polycythemic mouse bioassay. The ESF from the same supernatant can also be neutralized by anti-erythropoietin. A second concentrated supernatant fractionated using wheat germ lectin-Sepharose 6MB and compared to either unfractionated or fractionated step III erythropoietin (Ep), tested in vitro using the erythroid colony-forming technique and 12-day fetal liver as target cells, indicates parallelism of all linear dose-response lines. This, together with the in vivo data, strongly suggests that the ESF released from macrophages treated with silica is, in fact, Ep. Substituting Ca2+ ions for fetal calf serum in the preincubation procedure results in the same activity being released compared to the presence of 1% or 20% fetal calf serum.
D000818:Animals; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012822:Silicon Dioxide / Q000633:toxicity*
D004921:Erythropoietin; D012822:Silicon Dioxide