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

Increased Concentration of Iodide in Airway Secretions Is Associated with Reduced Respiratory Syncytial Virus Disease Severity

“…Blood (8 ml) was drawn from the external jugular vein, and serum was collected. Nasal secretions were collected with microsampling probes (BC-402C; Olympus, Center Valley, PA) as previously described (24,32). Nasal fluid was recovered from the microsampling probes by microcentrifugation.…”

“…Nasal fluid was recovered from the microsampling probes by microcentrifugation. Serum samples and nasal secretions were diluted in water and analyzed for anion composition using ionexchange chromatography as described previously (24,32).…”

“…Nasal secretions and serum samples were collected at 0 hours (just before the intragastric gavage) and at 4, 12, and 36 hours. At 4 and 12 hours, one animal per time point was killed after the collection of serum and nasal secretions to harvest tracheobronchial secretions as previously described (24,32). The remaining three animals were killed at 36 hours for the collection of tracheobronchial secretions.…”

Selective Metabolism of Hypothiocyanous Acid by Mammalian Thioredoxin Reductase Promotes Lung Innate Immunity and Antioxidant Defense

“…Interestingly, CFTR is also a major characterized apical transporter of SCN in the airway (46). Some studies have found decreased SCN in CF secretions and positively correlated SCN levels with lung function (17,41,47). Because even small changes in SCN concentration can dramatically affect the oxidant production of MPO and other haloperoxidases (3), deficient apical SCN transport could dramatically change the outcomes of infection and inflammation in the airway by shifting toward HOCl production, resulting in worse tissue inflammation and injury.…”

Uric Acid and Thiocyanate as Competing Substrates of Lactoperoxidase

“…However, it is clear from this work that urate and thiocyanate should be considered as competing physiological substrates for LPO. They are present in airway lining fluids at largely varying concentration ranges (urate: 40 -370 M, thiocyanate: 50 -400 M) (19,69), so they will compete for oxidation by compound I. It is likely that under most circumstances thiocyanate is the preferred substrate for compound I and urate will act simply by preventing accumulation of compound II and maintaining production of hypothiocyanite.…”