Evidence for an erythroblast-enhancing factor (EEF) in human and mouse serum.
Evidence accumulated over the past 20 years suggests that factors besides erythropoietin (Ep) may play a significant role in regulating mammalian erythropoiesis in vivo. These include moieties with both stimulatory and inhibitory activities. In this report data are summarized that demonstrate the presence of an erythropoietic stimulator in human and mouse serum that is distinct from Ep, burst-enhancing factor, albumin, or iron-saturated transferrin. Like Ep, this factor causes a significant increase in the amount of 59Fe incorporation into heme in vitro when 24-hr cultures of mouse marrow cells are used, but, unlike Ep, it has no effect in stimulating 59Fe uptake into red blood cells in vivo when injected alone into polycythemic mice. This differential effect with the two assays appears to reflect differences in the makeup of the erythroid progenitor cell compartments in polycythemic and normal mouse bone marrow. However, in both the in vitro and in vivo assays this factor acts synergistically with Ep to cause a dramatic stimulation of 59Fe incorporation. This non-Ep stimulator has been partially purified and appears to be a 130K protein with an isoelectric point of 4.8. For maximal activity, it appears to require substantially higher levels of iron-saturated transferrin than Ep. In addition, colcemid and time-course studies suggest that it acts late in erythroid differentiation, primarily on erythroblasts; hence, the term erythroblast-enhancing factor (EEF) has been proposed. Finally, serum EEF levels were found to vary in both mice and man in a predictable fashion, reflecting physiologic requirements for mature red blood cells. These last findings suggest that EEF acts as a positive regulator of terminal erythropoiesis in vivo.
D000818:Animals; D001798:Blood Proteins / Q000302:isolation & purification / Q000502:physiology*; D004900:Erythroblasts / Q000502:physiology*; D004920:Erythropoiesis; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D051379:Mice
D001798:Blood Proteins; D006133:Growth Substances