EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress.
Erythropoiesis is a robust process of cellular expansion and maturation occurring in murine bone marrow and spleen. We previously determined that sublethal irradiation, unlike bleeding or hemolysis, depletes almost all marrow and splenic erythroblasts but leaves peripheral erythrocytes intact. To better understand the erythroid stress response, we analyzed progenitor, precursor, and peripheral blood compartments of mice post-4 Gy total body irradiation. Erythroid recovery initiates with rapid expansion of late-stage erythroid progenitors-day 3 burst-forming units and colony-forming units, associated with markedly increased plasma erythropoietin (EPO). Although initial expansion of late-stage erythroid progenitors is dependent on EPO, this cellular compartment becomes sharply down-regulated despite elevated EPO levels. Loss of EPO-responsive progenitors is associated temporally with a wave of maturing erythroid precursors in marrow and with emergence of circulating erythroid progenitors and subsequent reestablishment of splenic erythropoiesis. These circulating progenitors selectively engraft and mature in irradiated spleen after short-term transplantation, supporting the concept that bone marrow erythroid progenitors migrate to spleen. We conclude that sublethal radiation is a unique model of endogenous stress erythropoiesis, with specific injury to the extravascular erythron, expansion and maturation of EPO-responsive late-stage progenitors exclusively in marrow, and subsequent reseeding of extramedullary sites.
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642, USA.
Scott A
SA
Peslak
Jesse
J
Wenger
Jeffrey C
JC
Bemis
Paul D
PD
Kingsley
Anne D
AD
Koniski
Kathleen E
KE
McGrath
James
J
Palis
D000818:Animals; D001853:Bone Marrow / Q000473:pathology* / Q000528:radiation effects; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D017707:Erythrocyte Transfusion; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000528:radiation effects; D004920:Erythropoiesis / Q000502:physiology* / Q000528:radiation effects; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology* / Q000528:radiation effects; D013234:Stem Cells; D014916:Whole-Body Irradiation
D004921:Erythropoietin