Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: Role of pendrin and anion channels

SCN- (thiocyanate) is an important physiological anion involved in innate defense of mucosal surfaces. SCN- is oxidized by H2O2, a reaction catalyzed by lactoperoxidase, to produce OSCN- (hypothiocyanite), a molecule with antimicrobial activity. Given the importance of the availability of SCN- in the airway surface fluid, we studied transepithelial SCN- transport in the human bronchial epithelium. We found evidence for at least three mechanisms for basolateral to apical SCN- flux. cAMP and Ca2+ regulatory pathways controlled SCN- transport through cystic fibrosis transmembrane conductance regulator and Ca2+-activated Cl- channels, respectively, the latter mechanism being significantly increased by treatment with IL-4. Stimulation with IL-4 also induced the strong up-regulation of an electroneutral SCN-/Cl- exchange. Global gene expression analysis with microarrays and functional studies indicated pendrin (SLC26A4) as the protein responsible for this SCN- transport. Measurements of H2O2 production at the apical surface of bronchial cells indicated that the extent of SCN- transport is important to modulate the conversion of this oxidant molecule by the lactoperoxidase system. Our studies indicate that the human bronchial epithelium expresses various SCN- transport mechanisms under resting and stimulated conditions. Defects in SCN- transport in the airways may be responsible for susceptibility to infections and/or decreased ability to scavenge oxidants.