Rapid myeloid growth induced by whole-body radioadaptive response

Abstract

We investigated the mechanism underlying the radioadaptive response that rescues low-dose preirradiated mice from hematopoietic failure after challenge irradiation. C57BL/6 mice were irradiated with low-dose acute X rays (0.5Gy) prior to a high-dose challenge irradiation. Bone marrow cells, erythrocytes and platelets in low-dose-preirradiated mice showed a rapid recovery following the challenge irradiation compared to those in mice subjected only to the challenge irradiation. This suggests that hematopoiesis following the challenge irradiation could be enhanced in the preirradiated mice. The rapid recovery of bone marrow cells following the challenge irradiation was consistent with the proliferation of hematopoietic progenitors expressing the cell surface markers c-kit⁺, Sca-1^- and Lin^- in low-dose-preirradiated mice. A subpopulation of myeloid (Mac-1⁺/Gr-1⁺) cells, which were descendants of c-kit⁺, Sca-1^- and Lin^- cells, more rapidly recovered in the bone marrow of low-dose-preirradiated mice. Cytokine profiles analysis by using antibody arrays and quantitative suspension arrays indicated that the concentrations of growth factors for myelopoiesis and of interferons after the challenge irradiation were considerably increased by low-dose preirradiation. The rapid recovery of erythrocytes and platelets suggests that low-dose preirradiation triggers the differentiation to myelopoietic cells. Thus the adaptive response induced by low-dose preirradiation in terms of the recovery kinetics of the number of hematopoietic cells may be due to the rapid recovery of the number of myeloid cells after high-dose irradiation.