Development of response to erythropoietin and repletion of the stem cell compartment after irradiation.

Abstract

Abstract Experiments involving repression of erythropoiesis by plethora, its partial restoration by erythropoietin, and assay of plasma erythropoietic activity provided evidence that erythropoietin was present in the plasma of mice after partial-body irradiation (850 R L.S.). Erythroblast counts and femoral uptake of 59 Fe disclosed that erythro-poietin-responsive cells increased in shielded femoral marrow initially but diminished to subnormal levels after 5 days. In contrast, replicating cells in the spleen were not responsive to erythropoietin until 5 days after irradiation, when increasing erythroblast counts and the splenic uptake of 59 Fe revealed their presence. Up to a point, the greater the number of endogenous stem cells permitted to emigrate from a shielded femur and colonize the spleen, the earlier will be the recovery of splenic erythropoiesis. The onset of splenic erythropoiesis was more closely related to the duration of leg-shielding and the mean splenic weight than it was to time elapsed after irradiation. We suggest that the new colonies of primitive hemopoietic cells must attain a certain critical mass before they develop the capacity to respond to erythropoietin by differentiation.