Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation

• Published in: The European respiratory journal Vol. 35; no. 6; pp. 1264 - 1272
• Main Authors: McKeon, D. J., Cadwallader, K. A., Idris, S., Cowburn, A. S., Pasteur, M. C., Barker, H., Haworth, C. S., Bilton, D., Chilvers, E. R., Condliffe, A. M.
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.06.2010
• Subjects: Adult; Biological and medical sciences; Blotting, Western; Cystic Fibrosis - immunology; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Errors of metabolism; Female; Gene Expression - immunology; Humans; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; NADPH Oxidases - metabolism; Neutrophils - immunology; Neutrophils - metabolism; Phosphoproteins - metabolism; Pneumology; Pneumonia - immunology; Pneumonia - metabolism; Reactive Oxygen Species - immunology; Reactive Oxygen Species - metabolism; Respiratory Burst - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Oxygen; Enzyme; Respiratory disease; Granulocyte; Oxidase; Metabolic diseases; Cystic fibrosis; Inflammation; Genetic disease; NADPH oxidase; Digestive diseases; Oxidoreductases; Neutrophil; Cystic fibrosis transmembrane conductance regulator; Pancreatic disease; Pneumology
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00089709

Previous studies have identified abnormalities in the oxidative responses of the neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or to the inflammatory environment present in this disease. The aim of the present study was to determine whether neutrophils from CF patients demonstrate an intrinsic abnormality of the respiratory burst. The respiratory burst activity of neutrophils isolated from stable ΔF508 homozygote CF patients and matched healthy controls was quantified by both chemiluminscence and cytochrome C reduction. Expression of NADPH oxidase components and CFTR was determined by Western blotting and RT-PCR. The oxidative output from neutrophils from CF in response to receptor-linked and particulate stimuli did not differ from that of controls. Expression of NADPH oxidase components was identical in CF and non-CF neutrophils. While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates. CFTR has no role in controlling neutrophil oxidative activity; previously reported differences in neutrophil function between CF and non-CF subjects most likely relate to the inflammatory milieu from which the cells were isolated.