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Updated: Nov 1, 2025
Morphological and Compositional Analysis of Neutrophil Extracellular Traps Induced by Microbial and Chemical Stimuli
Published on: November 4, 2022
Phagocyte extracellular traps in children with neutrophilic airway inflammation
Paul T King1,2, Lovisa Dousha1,2, Nadeene Clarke3,4
1Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia.
Insights
Childhood lung infections show significant neutrophil extracellular traps (NETs) and macrophage extracellular traps (METs). Treatments like deoxyribonuclease 1 and alpha1-antitrypsin can reduce these inflammatory markers in children.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pediatrics
Background:
- Childhood lung infections feature neutrophilic airway inflammation and elevated proteases like neutrophil elastase (NE).
- Neutrophil extracellular traps (NETs) and macrophage extracellular traps (METs) are implicated in inflammatory processes but their role in pediatric lung infections is not fully understood.
Purpose of the Study:
- To quantify NET and MET expression in children with cystic fibrosis and chronic cough.
- To investigate the effects of deoxyribonuclease 1 (DNase 1) and alpha1-antitrypsin (AAT) on NET/MET formation and neutrophil elastase activity.
Main Methods:
- Studied 76 children undergoing bronchoscopy, measuring NETs, METs, and NE activity in bronchoalveolar lavage (BAL) samples.
- Utilized confocal microscopy and functional assays to analyze extracellular traps and protease activity.
- Examined the in vitro effects of DNase 1 and AAT on NET/MET expression and NE activity.
Main Results:
- Both cystic fibrosis and non-cystic fibrosis groups exhibited significant airway neutrophilia with prominent NETs and co-expressed NE.
- NET expression correlated with detectable NE activity.
- DNase 1 reduced NET/MET expression but increased NE activity, while the combination of AAT and DNase 1 effectively reduced NE activity.
Conclusions:
- Symptomatic children, with or without cystic fibrosis, display prominent extracellular trap formation.
- This innate inflammatory response can be modulated by combining DNase 1 and AAT, suggesting therapeutic potential.
Abstract:
Childhood lung infection is often associated with prominent neutrophilic airway inflammation and excess production of proteases such as neutrophil elastase (NE). The mechanisms responsible for this inflammation are not well understood. One potentially relevant pathway is the production of extracellular traps by neutrophils (NETs) and macrophages (METs). The aim of this study was to measure NET and MET expression in children and the effect of deoxyribonculease (DNase) 1 and α1-antitrypsin (AAT) on this process. We studied 76 children (median age of 4.0 years) with cystic fibrosis or chronic cough who underwent investigational bronchoscopy. NETs, METs and neutrophil elastase activity in bronchoalveolar lavage (BAL) samples were measured using confocal microscopy and functional assays. The effects of DNase 1 and AAT on NET/MET expression and neutrophil elastase activity were examined in vitro. Both subject groups had airway neutrophilia with prominent BAL production of NETs with neutrophil elastase co-expression; the mean %±standard error of the mean of neutrophils expressing NETs in the cystic fibrosis group was 23.3±2.8% and in the non-cystic fibrosis group was 28.4±3.9%. NET expression was higher in subjects who had detectable neutrophil elastase activity (p≤0.0074). The percentage of macrophages expressing METs in the cystic fibrosis group was 10.7±1.2% and in the non-cystic fibrosis group was 13.2±1.9%. DNase 1 decreased NET/MET expression (p<0.0001), but increased neutrophil elastase activity (p≤0.0137). The combination of AAT and DNase 1 reduced neutrophil elastase activity (p≤0.0049). We observed prominent extracellular trap formation in symptomatic children with and without cystic fibrosis. This innate inflammatory response was down-regulated by a combination of currently available therapeutics.
