Conclusions
Micronucleated reticulocyte loss after higher sublethal radiation exposures results from rapid depletion of erythroid progenitors and precursors. This injury reveals that erythroid colony-forming units and proerythroblasts constitute a particularly proapoptotic compartment within the erythron. We conclude that the functional transition of primary proerythroblasts to later-stage erythroid precursors is characterized by a shift from a proapoptotic to an antiapoptotic phenotype.
Methods
We analyzed the response to 1 and 4 Gy total body irradiation of erythroid progenitors and precursors using colony assays and imaging flow cytometry, respectively. We also investigated cell cycling and apoptotic gene expression of the steady-state erythron.
Objective
Clastogenic injury of the erythroid lineage
Results
After 1 Gy total body irradiation, erythroid progenitors and precursors were partially depleted. In contrast, essentially all bone marrow erythroid progenitors and precursors were lost within 2 days after 4 Gy irradiation. Imaging flow cytometry analysis revealed preferential loss of phenotypic erythroid colony-forming units and proerythroblasts immediately after sublethal irradiation. Furthermore, these populations underwent radiation-induced apoptosis, without changes in steady-state cellular proliferation, at much higher frequencies than later-stage erythroid precursors. Primary erythroid precursor maturation is associated with marked Bcl-xL upregulation and Bax and Bid downregulation. Conclusions: Micronucleated reticulocyte loss after higher sublethal radiation exposures results from rapid depletion of erythroid progenitors and precursors. This injury reveals that erythroid colony-forming units and proerythroblasts constitute a particularly proapoptotic compartment within the erythron. We conclude that the functional transition of primary proerythroblasts to later-stage erythroid precursors is characterized by a shift from a proapoptotic to an antiapoptotic phenotype.