Reactive Oxygen Species in Macrophages: Sources and Targets.
Reactive Oxygen Species in Macrophages: Sources and Targets.
复制标题
DOI：
10.3389/fimmu.2021.734229
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Castegna A
中科院分区：
文献类型：
--
作者：
Canton M;Sánchez-Rodríguez R;Spera I;Venegas FC;Favia M;Viola A;Castegna A
活性氧（ROS）是巨噬细胞清除入侵微生物的基础。然而，正如在非吞噬细胞中观察到的，ROS在不同于病原体杀伤的过程中发挥重要作用，如信号转导、分化和基因表达。这些事件的不同结果可能取决于ROS形成的特定亚细胞位点，以及ROS产生的持续时间和程度。虽然ROS的过度积累长期以来一直被认为是有害的，但现在对它们作为信号分子的作用有了更深入的了解。这可以解释用全球抗氧化剂治疗几种疾病的“全或无”药理学方法的失败。NADPH氧化酶是已在巨噬细胞中鉴定的ROS的第一个来源。然而，越来越多的证据强调线粒体是这些细胞中ROS形成的关键部位，主要是由于呼吸链的电子泄漏或酶，如单胺氧化酶。它们在氧化还原信号传导中的作用，以及它们的确切形成位点仅部分阐明。因此，必须确定ROS的特定细胞内来源以及它们如何影响生理和病理条件下的细胞过程，以开发靶向氧化信号网络的疗法。在这篇综述中，我们将重点关注ROS在巨噬细胞中形成的不同位点以及它们如何影响代谢过程和炎症信号，突出线粒体与非线粒体ROS源相比的作用。
Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles in processes that are different from pathogen killing, as signal transduction, differentiation, and gene expression. The different outcomes of these events are likely to depend on the specific subcellular site of ROS formation, as well as the duration and extent of ROS production. While excessive accumulation of ROS has long been appreciated for its detrimental effects, there is now a deeper understanding of their roles as signaling molecules. This could explain the failure of the “all or none” pharmacologic approach with global antioxidants to treat several diseases. NADPH oxidase is the first source of ROS that has been identified in macrophages. However, growing evidence highlights mitochondria as a crucial site of ROS formation in these cells, mainly due to electron leakage of the respiratory chain or to enzymes, such as monoamine oxidases. Their role in redox signaling, together with their exact site of formation is only partially elucidated. Hence, it is essential to identify the specific intracellular sources of ROS and how they influence cellular processes in both physiological and pathological conditions to develop therapies targeting oxidative signaling networks. In this review, we will focus on the different sites of ROS formation in macrophages and how they impact on metabolic processes and inflammatory signaling, highlighting the role of mitochondrial as compared to non-mitochondrial ROS sources.