Concentration of the antibacterial precursor thiocyanate in cystic fibrosis airway secretions

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-Delta F508 homozygous pigs and control littermates. In the nasal ASL, the SCN- concentration was similar to 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-. (C) 2011 Elsevier Inc. All rights reserved.