Vorobjeva N V
Department of Biology, Moscow State University, 119234 Moscow, Russia.
Moscow Univ Biol Sci Bull. 2020;75(4):173-188. doi: 10.3103/S0096392520040112. Epub 2021 Feb 8.
Neutrophils are the "first line" of defense against pathogens in the locus of inflammation, where they use effector functions such as phagocytosis, degranulation, and formation of reactive oxygen species (ROS). In 2004, Artuto Zychlinsky characterized one more neutrophil effector function-the release of neutrophil extracellular traps (or NETs). NETs are a modified chromatin "decorated" by bactericidal proteins of granules, nucleus, and cytoplasm. The release of NETs can be activated by diverse physiological and pharmacological stimuli and depends on ROS, for which NADPH oxidase is the main source. In the process of NET formation, the release of bactericidal components of granules into the cytoplasm, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope and cytoplasmic membrane with the involvement of gasdermin D protein, and, finally, the release of chromatin outside the cell occurs. At the same time, uncontrolled formation of NETs is a provoking factor in the development of many inflammatory and autoimmune diseases. NETs were found at autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and vasculitis; NETs are involved in the pathogenesis of cardiovascular, pulmonary, and oncological diseases. In this review, the main ideas about the mechanisms of NET formation, as well as their role in physiological processes and pathogenesis of a number of diseases (including COVID-19), are discussed.
中性粒细胞是炎症部位抵御病原体的“第一道防线”,它们在此发挥吞噬作用、脱颗粒作用以及产生活性氧(ROS)等效应功能。2004年,阿尔图托·齐克林斯基又发现了中性粒细胞的一种效应功能——释放中性粒细胞胞外诱捕网(NETs)。NETs是一种经过修饰的染色质,由颗粒、细胞核和细胞质中的杀菌蛋白“装饰”而成。NETs的释放可被多种生理和药理刺激激活,且依赖于ROS,NADPH氧化酶是ROS的主要来源。在NET形成过程中,颗粒中的杀菌成分释放到细胞质中,组蛋白发生修饰导致染色质解聚,在gasdermin D蛋白的参与下核膜和细胞质膜被破坏,最终染色质释放到细胞外。与此同时,NETs的失控形成是许多炎症和自身免疫性疾病发展的诱发因素。在系统性红斑狼疮、类风湿性关节炎、银屑病和血管炎等自身免疫性疾病中发现了NETs;NETs参与心血管疾病、肺部疾病和肿瘤疾病的发病机制。在这篇综述中,讨论了关于NET形成机制的主要观点,以及它们在生理过程和多种疾病(包括COVID-19)发病机制中的作用。