Image: Flickr - Clayirving Cystic Fibrosis (CF) is an autosomal recessive genetic disorder affecting the secretory glands, resulting from mutations in the CF transmembrane conductance regulator (CFTR) gene. The disease predominantly involves the respiratory and digestive systems, with lung injuries and infections responsible for approximately 90% of the morbidity and mortality of CF patients.
CFTR encodes a chloride conducting channel and the CF-causing mutations result in reduced numbers and/or defective ion channels. Although the link between mutated CFTR and CF has been known for 20 years, the fundamental question of how this results in disease has remained elusive. Contrary to expectations, the levels of Cl– in the airways of CF patients are not very different to those found in unaffected individuals.
It is known, however, that CFTR channels are able to conduct other ions, including thiocyanate (SCN–), and new research from scientists at the Howard Hughes Medical Institute and University of Pennsylvania School of Medicine now suggests that defective SCN– transport may play a role. Thiocyanate has antioxidant properties, providing protection from reactive oxygen species (ROS) that are formed in response to infection. Transport of thiocyanate into the airway lumen results in higher concentrations in airway secretions than in plasma and is dependent on functional CFTR. In this study, the researchers showed that lactoperoxidase in the airways catalyses the conversion of SCN– to tissue-innocuous hypothiocyanite (OSCN–), consuming potentially damaging hydrogen peroxide in the process. Further, SCN– depletes harmful hypochlorite (OCl–) through competition with chloride ion for myeloperoxidase and by direct reduction.
The authors of the study, published in PNAS, suggest that as well as a potential role in the pathogenesis of CF, insufficient levels of SCN– may provide inadequate protection from hypochlorite, exacerbating inflammatory diseases.