Targeting neutrophil extracellular traps (NETs): a promising immunotherapeutic approach for pulmonary diseases.

Chronic lung disease, a major cause of death worldwide, is characterized by persistent lung inflammation and the infiltration of inflammatory cells that include neutrophils, macrophages, and so on. When activated by pathogens, neutrophils engage a unique immunological mechanism known as NETosis, which releases neutrophil extracellular traps (NETs) via both lytic and non-lytic pathways. NETs are web-like structures composed of DNA and histones (H1, H2A, H2B, H3, and H4) that are embedded with a variety of antimicrobial proteins. In innate immunity, the primary function of NETs is to prevent and eliminate harmful microbes from the human body. However, excessive NET formation and insufficient clearance contribute to thrombotic inflammation and lung tissue destruction, which have emerged as key modulators of many lung disorders such as asthma, pulmonary arterial hypertension, chronic obstructive pulmonary disease, lung cancer, and idiopathic pulmonary fibrosis. Therapeutic strategies that target the formation mechanisms and biomarkers of NETs may hold potential for future clinical translation. This review focuses on the mechanisms of NET formation, elucidates the potential pathogenic role of NETs in a variety of lung diseases, and discusses drugs that may inhibit NETs, providing a promising therapeutic approach for the treatment of lung diseases.