Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, 732-0815, Japan.
Biostatistics Center, Kurume University, Kurume, 830-0011, Japan.
Free Radic Biol Med. 2021 Aug 1;171:126-134. doi: 10.1016/j.freeradbiomed.2021.05.017. Epub 2021 May 14.
Although reactive oxygen species (ROS) play important roles in immune responses, excessive ROS production and accumulation might enhance the risk of inflammation-related diseases. Moreover, impaired immune function and the acceleration of pre-clinically persistent inflammation due to aging and radiation exposure have been observed in atomic bomb (A-bomb) survivors more than 60 years post-exposure. Meanwhile, the effects of aging and radiation exposure on ROS production in immune cells have not been characterized. This study investigated the relationship between intracellular ROS (HO and O) levels in blood cells or T cell subsets and serum iron, ferritin, and C-reactive protein (CRP) levels, as well as how these variables are affected by age and radiation exposure in A-bomb survivors. We examined 2495 Hiroshima A-bomb survivors. Multiple linear regression models adjusted for confounding factors indicated that intracellular O levels in monocytes, granulocytes, and lymphocytes, and particularly in memory CD8 T cells, including effector memory and terminally differentiated effector memory CD8 T cells, increased with radiation dose. Additionally, serum iron, ferritin, and CRP levels affected intracellular ROS levels in specific blood cell types and T cell subsets. Serum CRP levels increased significantly with increasing age and radiation dose. Finally, when divided into three groups according to serum CRP levels, dose-dependent increases in the intracellular O levels in blood cells and central memory and effector memory CD8 T cells were most prominently observed in the high-CRP group. These results suggest that an increase in the levels of certain intracellular ROS, particularly after radiation exposure, might be linked to enhanced inflammatory status, including elevated serum CRP levels and reduced serum iron levels. This study reveals that aging and radiation exposure increase oxidative stress in blood cells, which is involved in impaired immune function and accelerated pre-clinically persistent inflammation in radiation-exposed individuals.
虽然活性氧（ROS）在免疫反应中发挥着重要作用，但过量的 ROS 产生和积累可能会增加炎症相关疾病的风险。此外，在遭受原子弹（A 炸弹）辐射超过 60 年后的幸存者中，已经观察到免疫功能受损和由于衰老和辐射暴露导致的临床前持续炎症加速。同时，衰老和辐射暴露对免疫细胞中 ROS 产生的影响尚未得到描述。本研究调查了血细胞或 T 细胞亚群中细胞内 ROS（HO 和 O）水平与血清铁、铁蛋白和 C 反应蛋白（CRP）水平之间的关系，以及这些变量如何受 A 炸弹幸存者年龄和辐射暴露的影响。我们检查了 2495 名广岛 A 炸弹幸存者。经过混杂因素调整的多元线性回归模型表明，单核细胞、粒细胞和淋巴细胞，特别是记忆 CD8 T 细胞（包括效应记忆和终末分化效应记忆 CD8 T 细胞）中的细胞内 O 水平随辐射剂量增加而增加。此外，血清铁、铁蛋白和 CRP 水平影响特定血细胞类型和 T 细胞亚群中的细胞内 ROS 水平。血清 CRP 水平随年龄和辐射剂量的增加而显著增加。最后，根据血清 CRP 水平将幸存者分为三组，在高 CRP 组中，血细胞和中央记忆及效应记忆 CD8 T 细胞中细胞内 O 水平的剂量依赖性增加最为显著。这些结果表明，某些细胞内 ROS 水平的增加，特别是在辐射暴露后，可能与增强的炎症状态有关，包括血清 CRP 水平升高和血清铁水平降低。本研究揭示了衰老和辐射暴露会增加血细胞中的氧化应激，这与辐射暴露个体免疫功能受损和临床前持续炎症加速有关。
