RT Journal Article
SR Electronic
T1 Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 449
OP 458
DO 10.1136/thoraxjnl-2019-214027
VO 75
IS 6
A1 Zivile Useckaite
A1 Mark P Ward
A1 Anne Trappe
A1 Rebecca Reilly
A1 Jenny Lennon
A1 Holly Davage
A1 David Matallanas
A1 Hilary Cassidy
A1 Eugene T Dillon
A1 Kiva Brennan
A1 Sarah L Doyle
A1 Suzanne Carter
A1 Seamas Donnelly
A1 Barry Linnane
A1 Edward F McKone
A1 Paul McNally
A1 Judith A Coppinger
YR 2020
UL http://thorax.bmj.com/content/75/6/449.abstract
AB Rationale Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways.Objectives To investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF.Methods EVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs.Results A significantly higher level of EVs were released from CFBE41o- (p<0.0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p<0.001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p<0.001–0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls.Conclusion This study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF.