Taurine modulation of hypochlorous acid-induced lung epithelial cell injury in vitro. Role of anion transport.
Airway secretions of cystic fibrosis patients were found to contain high concentrations of taurine, which decreased with antibiotic therapy during acute respiratory exacerbations. Taurine, in a 1:1 molar ratio with HOCl/OCl-, caused a 10-fold increase in the amount of HOCl/OCl- needed to induce cytotoxicity to the cat lung epithelial cell line, AKD. Although DMSO protected cells against HOCl/OCl(-)-mediated injury, the presence of an equimolar concentration of taurine with HOCl/OCl- prevented DMSO from protecting cells and sulfhydryl groups against oxidation, suggesting the formation of taurine chloramines. Spectral properties confirmed the formation of monochloramines and dichloramines. Chloride-free buffer, DIDS, and low temperature (4 degrees C) each protected the cells against taurine/HOCl/OCl-, indicating that taurine chloramine uptake through anion transport pathways was required to induce cytotoxicity. A molar excess of taurine inhibited cytotoxicity, to induce cytotoxicity. A molar excess of taurine inhibited cytotoxicity, by decreasing taurine dichloramines and increasing the formation of less toxic taurine monochloramines. We conclude that taurine can protect lung epithelial cells by converting HOCl/OCl- to anionic monochloramines, but that taurine dichloramines can be toxic to respiratory epithelial cells through mechanisms that depend upon epithelial cell anion transport.
Cantin
A M
AM
Unité de Recherche Pulmonaire, Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D000838:Anions / Q000378:metabolism; D001991:Bronchitis / Q000473:pathology; D002415:Cats; D002460:Cell Line; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D012016:Reference Values; D012907:Smoking / Q000473:pathology; D013654:Taurine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D013696:Temperature
D000838:Anions; D013654:Taurine; C043410:N-chlorotaurine; D006997:Hypochlorous Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D004121:Dimethyl Sulfoxide