The role of netosis in the pathogenesis of respiratory diseases

Abstract

Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA and antimicrobial proteins released by activated neutrophils during NETosis. This review aims to systematically analyze the role of NETosis in the pathogenesis of respiratory diseases and evaluate potential therapeutic strategies. We discuss the mechanisms of NETosis (lytic and vital), the dual function of NETs — ranging from antimicrobial defense to mediating tissue damage — as well as current detection. Particular emphasis is placed on the role of NETosis in COVID-19, bronchial asthma (specifically neutrophilic phenotypes), chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Therapeutic approaches targeting the modulation and inhibition of NETosis are discussed, including DNase I, protease inhibitors, phosphodiesterase-4 (PDE4) inhibitors, dipeptidyl peptidase-1 (DPP-1) inhibitors, and biological therapies. Analysis of 55 publications retrieved from PubMed and eLibrary confirms that NETosis is a central pathogenetic mechanism rather than solely a biomarker. This positions NETs as a promising therapeutic target, despite disease heterogeneity and the complexity of NETosis regulation. The review also summarizes research findings on NET detection and visualization, mechanisms of NET formation in respiratory pathology, animal modeling of disease states, and the subsequent application of targeted therapies directed against NET components.