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 H(2)O(2), 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 Ca(2+) regulatory pathways controlled SCN(-) transport through cystic fibrosis transmembrane conductance regulator and Ca(2+)-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 H(2)O(2) 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.
Pedemonte
Nicoletta
N
Laboratory of Molecular Genetics, Istituto Giannina Gaslini, Genova, Italy.
Caci
Emanuela
E
Sondo
Elvira
E
Caputo
Antonella
A
Rhoden
Kerry
K
Pfeffer
Ulrich
U
Di Candia
Michele
M
Bandettini
Roberto
R
Ravazzolo
Roberto
R
Zegarra-Moran
Olga
O
Galietta
Luis J V
LJ
D000818:Animals; D001692:Biological Transport; D001980:Bronchi / Q000378:metabolism*; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D000076988:Sulfate Transporters; D013861:Thiocyanates / Q000378:metabolism*
D018118:Chloride Channels; D002712:Chlorides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D013861:Thiocyanates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015847:Interleukin-4; D006861:Hydrogen Peroxide; C031760:thiocyanate