The Role of Reactive Oxygen Species (ROS) in the Formation of Extracellular Traps (ETs) in Humans.
The Role of Reactive Oxygen Species (ROS) in the Formation of Extracellular Traps (ETs) in Humans.
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DOI：
10.3390/biom5020702
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发表时间：
2015-05-04
期刊：
影响因子：
5.5
通讯作者：
Krautgartner WD
中科院分区：
文献类型：
--
作者：
Stoiber W;Obermayer A;Steinbacher P;Krautgartner WD
细胞外陷阱(ETS)是与抗菌分子相关的胞外DNA的网状结构。它们由吞噬细胞(主要是中性粒细胞：Net)形成，已被认为是脊椎动物天然免疫防御的基本要素。然而，由于ETS对宿主细胞也有毒性，并能有效地触发自身免疫，因此它们在病原体防御和人类发病机制之间的作用是模糊的，它们会导致多种急慢性炎症性疾病。自从十年前发现ET形成以来，越来越多的证据表明，导致ET释放的大多数反应级联反应都涉及ROS。一个重要的新方面是增加了一个重要的新方面，当很明显，内毒素血症可能直接联系到自噬细胞死亡途径，或它是自噬细胞死亡途径的变体。本综述分析了迄今为止关于ROS、自噬和ETsis之间相互作用的证据，并重点讨论了ROS-ET关系的几个不完全了解的进一步方面。这些方面包括NADPH氧化酶来源的ROS的作用，NADPH氧化酶依赖的ETsis的分子需求，NADPH氧化酶亚型的作用，细胞外ROS和NADPH氧化酶以外来源的ROS的作用，以及ROS非依赖性ETsis的现有证据。我们得出的结论是，ROS以多维的方式与ETori相互作用，影响ETori表现出有利还是有害的影响。
Extracellular traps (ETs) are reticulate structures of extracellular DNA associated with antimicrobial molecules. Their formation by phagocytes (mainly by neutrophils: NETs) has been identified as an essential element of vertebrate innate immune defense. However, as ETs are also toxic to host cells and potent triggers of autoimmunity, their role between pathogen defense and human pathogenesis is ambiguous, and they contribute to a variety of acute and chronic inflammatory diseases. Since the discovery of ET formation (ETosis) a decade ago, evidence has accumulated that most reaction cascades leading to ET release involve ROS. An important new facet was added when it became apparent that ETosis might be directly linked to, or be a variant of, the autophagy cell death pathway. The present review analyzes the evidence to date on the interplay between ROS, autophagy and ETosis, and highlights and discusses several further aspects of the ROS-ET relationship that are incompletely understood. These aspects include the role of NADPH oxidase-derived ROS, the molecular requirements of NADPH oxidase-dependent ETosis, the roles of NADPH oxidase subtypes, extracellular ROS and of ROS from sources other than NADPH oxidase, and the present evidence for ROS-independent ETosis. We conclude that ROS interact with ETosis in a multidimensional manner, with influence on whether ETosis shows beneficial or detrimental effects.