Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1714, USA.
Radiat Res. 2010 Apr;173(4):406-17. doi: 10.1667/RR1931.1.
The body senses "danger" from "damaged self" molecules through members of the same receptor superfamily it uses for microbial "non-self", triggering canonical signaling pathways that lead to the generation of acute inflammatory responses. For this reason, the biology of normal tissue responses to moderate and clinically relevant doses of radiation is inextricably connected to innate immunity. The complex sequence of inflammatory events that ensues causes further cell and tissue damage to eliminate potential invaders but also leads to cytoprotective responses that limit the spread of damage and to wound healing through tissue regeneration or replacement. These sequential processes are orchestrated through multiple feedback control mechanisms involving cyclical production of free radicals and cytokines that are common to both radiation and immune signaling. This requires a concerted effort by resident tissue and inflammatory cell types, with macrophages apparently leading the way. The initial response to moderate doses of radiation therefore feeds into a pro-inflammatory paradigm whose eventual outcome is critically dependent upon the properties of the immune cells that are involved in tissue damage, regeneration and repair and that are in part under genetic influence. Importantly, these canonical pathways provide targets for interventions aimed at modifying normal tissue radiation responses. In this review, we examine areas of intersection between innate immunity and normal tissue radiobiology.
人体通过其用于微生物“非自身”的相同受体超家族成员来感知“受损自身”分子的“危险”，触发导致急性炎症反应产生的经典信号通路。出于这个原因，正常组织对中等和临床相关剂量辐射的反应生物学与先天免疫密不可分。随后发生的复杂炎症事件序列会导致进一步的细胞和组织损伤，以消除潜在的入侵者，但也会导致细胞保护反应，限制损伤的扩散，并通过组织再生或替代进行伤口愈合。这些连续的过程通过涉及自由基和细胞因子的循环产生的多种反馈控制机制来协调，这些自由基和细胞因子在辐射和免疫信号中都很常见。这需要常驻组织和炎症细胞类型的协同努力，巨噬细胞显然处于领先地位。因此，中等剂量辐射的初始反应会导致促炎范式，其最终结果严重依赖于参与组织损伤、再生和修复的免疫细胞的特性，而这些特性部分受遗传影响。重要的是，这些经典途径为旨在改变正常组织辐射反应的干预措施提供了目标。在这篇综述中，我们研究了先天免疫与正常组织放射生物学之间的交叉领域。
