Extracellular vesicles in sputum of children with cystic fibrosis pulmonary exacerbations.
| Autor: | Ben-Meir E; Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.; Programs in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada., Antounians L; Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada., Eisha S; Programs in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada., Ratjen F; Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.; Programs in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada., Zani A; Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada.; Department of Surgery, University of Toronto, Toronto, ON, Canada., Grasemann H; Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.; Programs in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada. |
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| Jazyk: | angličtina |
| Zdroj: | ERJ open research [ERJ Open Res] 2024 Dec 09; Vol. 10 (6). Date of Electronic Publication: 2024 Dec 09 (Print Publication: 2024). |
| DOI: | 10.1183/23120541.00547-2024 |
| Abstrakt: | Background: The aim of this study was to quantify mediators of neutrophilic inflammation within airway extracellular vesicles (EVs) of children treated for a cystic fibrosis (CF) pulmonary exacerbation (PEx). Methods: EVs were isolated from stored sputum samples collected before and after antibiotic therapy for PEx between 2011 and 2013, and characterised by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Western blot analysis of EV protein extracts was used for EV canonical protein markers CD63, CD9 and flotillin-1 (FLOT1), as well as neutrophil elastase (NE), myeloperoxidase (MPO) and interleukin-8. The EV content of NE and MPO were expressed as ratios of NE/FLOT1 and MPO/FLOT1 protein band densities. Results: Sputum samples from 21 children aged 13.3 (range 8.0-17.0) years were analysed. NTA showed high concentrations of particles at the size of small EVs (50-200 nm), and typical EV morphology was confirmed by TEM. CD63, CD9 and FLOT1 were detectable in all samples. Median (interquartile range (IQR)) NE/FLOT1 increased from 2.46 (1.68-5.25) before to 6.83 (3.89-8.89, p<0.001) after PEx therapy, and median (IQR) MPO/FLOT1 increased from 2.30 (1.38-4.44) before to 5.76 (3.45-6.94, p<0.01) after, while EV size remained unchanged. Improvement in lung function (percent predicted forced expiratory volume in 1 s (ppFEV Conclusions: Airways of children with CF contain EVs that carry NE and MPO as cargo. The lower NE and MPO content at the time of PEx, compared with after therapy, and the correlation with pulmonary function suggest both a functional role of EVs in CF airway inflammation and the potential of EVs as a biomarker to monitor CF lung disease. Competing Interests: Conflict of interest: F. Ratjen reports receiving consulting fees from Vertex Pharmaceuticals outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose. (Copyright ©The authors 2024.) |
| Databáze: | MEDLINE |
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