Neutrophil Extracellular Traps: New Aspects

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.