NEUTROPHIL EXTRACELLULAR TRAP - DEFINITION, MOLECULAR MECHANISMS
Keywords:
NETs, neutrophils, proteinsAbstract
Innate immunity constitutes the body’s primary defense against invading pathogens and plays a crucial role in guiding adaptive immunity during persistent infections. Neutrophils employ three primary mechanisms to directly combat microorganisms: phagocytosis, degranulation, and the generation of neutrophil extracellular traps (NETs). Neutrophil extracellular traps (NETs) are intricate fibrous structures released by neutrophils in response to specific stimuli. These structures are composed of depolymerized chromatin adorned with histones, neutrophil granule proteins, including primary granules (neutrophil elastase (NE), myeloperoxidase (MPO), cathepsin G), secondary granules (lactoferrin and pentraxin 3), tertiary granules (matrix metalloproteinase - MMP), cytoplasmic components (calprotectin, catalase) and other enzymatically active proteases and peptides that have procoagulant properties. NETs are formed via two distinct pathways known as suicidal NETosis, which involves NADPH oxidase (NOX), and vital NETosis, which is independent of NOX. Three primary forms of NET release have been identified: suicidal NETosis, vital NETosis, and mitochondrial NETosis. Certain proteins found within NETs exhibit strong cytotoxic effects against both pathogens and nearby host cells. While NETs play a vital role in trapping and eliminating pathogens, pathogens have developed strategies to evade immune responses, prompting neutrophils to initiate more aggressive reactions. The excessive activation of NETs and the consequent pro-inflammatory response can result in severe tissue damage. The extremely important role of NETs in tumor biology, carcinogenesis and metastasis processes has been proven. Conclusion: This review summarises the current knowledge of neutrophils and NETs, the mechanisms that lead to the formation of NETs and significant implications in a wide range of diseases. The identification of NETs and the characterization of their role in disease have revived the overlooked role of neutrophils in disease pathogenesis..
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