Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy

Holly R. Keir (Lead / Corresponding author), James D. Chalmers

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)
31 Downloads (Pure)

Abstract

Neutrophilic inflammation has a key role in the pathophysiology of multiple chronic lung diseases. The formation of neutrophil extracellular traps (NETs) has emerged as a key mechanism of disease in neutrophilic lung diseases including asthma, COPD, cystic fibrosis and, most recently, bronchiectasis. NETs are large, web-like structures composed of DNA and anti-microbial proteins that are able to bind pathogens, prevent microbial dissemination and degrade bacterial virulence factors. The release of excess concentrations of proteases, antimicrobial proteins, DNA and histones, however, also leads to tissue damage, impaired mucociliary clearance, impaired bacterial killing and increased inflammation. A number of studies have linked airway NET formation with greater disease severity, increased exacerbations and overall worse disease outcomes across the spectrum of airway diseases. Treating neutrophilic inflammation has been challenging in chronic lung disease because of the delicate balance between reducing inflammation and increasing the risk of infections through immunosuppression. Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target. This review will discuss the relationship between NETs and the pathophysiology of cystic fibrosis, asthma, COPD and bronchiectasis, and explore the current and future development of NET-targeting therapies.

Original languageEnglish
Article number210241
Number of pages19
JournalEuropean Respiratory Review
Volume31
Issue number163
Early online date22 Feb 2022
DOIs
Publication statusPublished - 31 Mar 2022

Keywords

  • Asthma/metabolism
  • Bronchiectasis/metabolism
  • Cystic Fibrosis/metabolism
  • Extracellular Traps/metabolism
  • Humans
  • Neutrophils/metabolism

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