Phagocyte extracellular traps in children with neutrophilic airway inflammation
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 extracellu...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2021-06-01
|
| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/7/2/00883-2020.full |
| _version_ | 1819145693182296064 |
|---|---|
| author | Paul T. King Lovisa Dousha Nadeene Clarke Jennifer Schaefer Rosemary Carzino Roleen Sharma Ken L. Wan Aveena Anantharajah Kim O'Sullivan Zhong X. Lu Stephen R. Holdsworth Sarath Ranganathan Philip G. Bardin David S. Armstrong |
| author_facet | Paul T. King Lovisa Dousha Nadeene Clarke Jennifer Schaefer Rosemary Carzino Roleen Sharma Ken L. Wan Aveena Anantharajah Kim O'Sullivan Zhong X. Lu Stephen R. Holdsworth Sarath Ranganathan Philip G. Bardin David S. Armstrong |
| author_sort | Paul T. King |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T13:02:05Z |
| format | Article |
| id | doaj.art-117403dc98d74041be104999276d522c |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-12-22T13:02:05Z |
| publishDate | 2021-06-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-117403dc98d74041be104999276d522c2022-12-21T18:24:58ZengEuropean Respiratory SocietyERJ Open Research2312-05412021-06-017210.1183/23120541.00883-202000883-2020Phagocyte extracellular traps in children with neutrophilic airway inflammationPaul T. King0Lovisa Dousha1Nadeene Clarke2Jennifer Schaefer3Rosemary Carzino4Roleen Sharma5Ken L. Wan6Aveena Anantharajah7Kim O'Sullivan8Zhong X. Lu9Stephen R. Holdsworth10Sarath Ranganathan11Philip G. Bardin12David S. Armstrong13 Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia Paediatric Respiratory Medicine, Royal Children's Hospital, Melbourne, Australia Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia Paediatric Respiratory Medicine, Royal Children's Hospital, Melbourne, Australia Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia Dept of Biochemistry, Monash Pathology, Monash Health, Melbourne, Australia Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia Monash University Dept of Medicine, Monash Medical Centre, Melbourne, Victoria, Australia Monash University Dept of Medicine, Monash Medical Centre, Melbourne, Victoria, Australia Monash University Dept of Medicine, Monash Medical Centre, Melbourne, Victoria, Australia Paediatric Respiratory Medicine, Royal Children's Hospital, Melbourne, Australia Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia Monash Lung and Sleep, Monash Medical Centre, Melbourne, Australia 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.http://openres.ersjournals.com/content/7/2/00883-2020.full |
| spellingShingle | Paul T. King Lovisa Dousha Nadeene Clarke Jennifer Schaefer Rosemary Carzino Roleen Sharma Ken L. Wan Aveena Anantharajah Kim O'Sullivan Zhong X. Lu Stephen R. Holdsworth Sarath Ranganathan Philip G. Bardin David S. Armstrong Phagocyte extracellular traps in children with neutrophilic airway inflammation ERJ Open Research |
| title | Phagocyte extracellular traps in children with neutrophilic airway inflammation |
| title_full | Phagocyte extracellular traps in children with neutrophilic airway inflammation |
| title_fullStr | Phagocyte extracellular traps in children with neutrophilic airway inflammation |
| title_full_unstemmed | Phagocyte extracellular traps in children with neutrophilic airway inflammation |
| title_short | Phagocyte extracellular traps in children with neutrophilic airway inflammation |
| title_sort | phagocyte extracellular traps in children with neutrophilic airway inflammation |
| url | http://openres.ersjournals.com/content/7/2/00883-2020.full |
| work_keys_str_mv | AT paultking phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT lovisadousha phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT nadeeneclarke phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT jenniferschaefer phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT rosemarycarzino phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT roleensharma phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT kenlwan phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT aveenaanantharajah phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT kimosullivan phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT zhongxlu phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT stephenrholdsworth phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT sarathranganathan phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT philipgbardin phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation AT davidsarmstrong phagocyteextracellulartrapsinchildrenwithneutrophilicairwayinflammation |