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REVIEW: NETosis: Molecular Mechanisms, Role in Physiology and Pathology

N. V. Vorobjeva1,a* and B. V. Chernyak2,b

1Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

2Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

* To whom correspondence should be addressed.

Received June 20, 2020; Revised July 16, 2020; Accepted July 16, 2020
NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis. Induction of NETosis depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Activation of NADPH oxidase depends on increase in the concentration of Ca2+ in the cytoplasm and in some cases on the generation of ROS in mitochondria. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane. In this review, basic mechanisms of NETosis, as well as its role in the pathogenesis of some diseases including COVID-19 are discussed.
KEY WORDS: neutrophil, neutrophil extracellular traps, NETosis, NADPH oxidase, reactive oxygen species, mitochondrial pore, COVID-19

DOI: 10.1134/S0006297920100065