Deposition of Iron in the Bone Marrow of a Murine Model of Hematopoietic Acute Radiation Syndrome

作者：W. Bradley Rittase, Jeannie M. Muir, John E. Slaven, Roxane M. Bouten, Michelle A. Bylicky, William L. Wilkins, Regina M. Day · 发表于：Experimental Hematology · 年份：2020 · DOI：10.1016/j.exphem.2020.03.004 · 被引用次数：15 · 研究领域：Effects of Radiation Exposure、Immunotoxicology and immune responses、Vitamin C and Antioxidants Research

Exposure to high-dose total body irradiation (TBI) can result in hematopoietic acute radiation syndrome (H-ARS), characterized by leukopenia, anemia, and coagulopathy. Death from H-ARS occurs from hematopoietic insufficiency and opportunistic infections. Following radiation exposure, red blood cells (RBCs) undergo hemolysis from radiation-induced hemoglobin denaturation, causing the release of iron. Free iron can have multiple detrimental biological effects, including suppression of hematopoiesis. We investigated the impact of radiation-induced iron release on the bone marrow following TBI and the potential impact of the ACE inhibitor captopril, which improves survival from H-ARS. C57BL/6J mice were exposed to 7.9 Gy, 60 Co irradiation, 0.6 Gy/min (LD 70–90/30 ). RBCs and reticulocytes were significantly reduced within 7 days of TBI, with the RBC nadir at 14–21 days. Iron accumulation in the bone marrow correlated with the time course of RBC hemolysis, with an ∼10-fold increase in bone marrow iron at 14–21 days post-irradiation, primarily within the cytoplasm of macrophages. Iron accumulation in the bone marrow was associated with increased expression of genes for iron binding and transport proteins, including transferrin, transferrin receptor 1, ferroportin, and integrin αMβ2. Expression of the gene encoding Nrf2, a transcription factor activated by oxidative stress, also increased at 21 days post-irradiation. Captopril did not alter iron accumulation in the bone marrow or e...