title: Concentration of the antibacterial precursor thiocyanate in cystic fibrosis airway secretions.
abstract: A recently discovered enzyme system produces antibacterial hypothiocyanite (OSCN(-)) in the airway lumen by oxidizing the secreted precursor thiocyanate (SCN(-)). Airway epithelial cultures have been shown to secrete SCN(-) in a CFTR-dependent manner. Thus, reduced SCN(-) availability in the airway might contribute to the pathogenesis of cystic fibrosis (CF), a disease caused by mutations in the CFTR gene and characterized by an airway host defense defect. We tested this hypothesis by analyzing the SCN(-) concentration in the nasal airway surface liquid (ASL) of CF patients and non-CF subjects and in the tracheobronchial ASL of CFTR-ΔF508 homozygous pigs and control littermates. In the nasal ASL, the SCN(-) concentration was ~30-fold higher than in serum independent of the CFTR mutation status of the human subject. In the tracheobronchial ASL of CF pigs, the SCN(-) concentration was somewhat reduced. Among human subjects, SCN(-) concentrations in the ASL varied from person to person independent of CFTR expression, and CF patients with high SCN(-) levels had better lung function than those with low SCN(-) levels. Thus, although CFTR can contribute to SCN(-) transport, it is not indispensable for the high SCN(-) concentration in ASL. The correlation between lung function and SCN(-) concentration in CF patients may reflect a beneficial role for SCN(-).
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lorentzen
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Durairaj
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Pezzulo
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Janice
authors.initials: J
authors.lastname: Launspach
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.forename: Gideon
authors.initials: G
authors.lastname: Zamba
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: William M
authors.initials: WM
authors.lastname: Nauseef
authors.forename: Botond
authors.initials: B
authors.lastname: Bánfi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D012634:Bodily Secretions; D001980:Bronchi / Q000378:metabolism; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D008826:Microbial Sensitivity Tests; D009296:Nasal Cavity / Q000378:metabolism; D010084:Oxidation-Reduction; D013211:Staphylococcus aureus / Q000254:growth & development; D013552:Swine; D013861:Thiocyanates / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D013861:Thiocyanates; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C014607:hypothiocyanite ion; C031760:thiocyanate