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 hi gh 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- n eeded 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- prev ented DMSO from protecting cells and sulfhydryl groups against oxidati on, suggesting the formation of taurine chloramines. Spectral properti es confirmed the formation of monochloramines and dichloramines. Chlor ide-free buffer, DIDS, and low temperature (4 degrees C) each protecte d the cells against taurine/HOCl/OCl-, indicating that taurine chloram ine uptake through anion transport pathways was required to induce cyt otoxicity. A molar excess of taurine inhibited cytotoxicity, by decrea sing taurine dichloramines and increasing the formation of less toxic taurine monochloramines. We conclude that taurine can protect lung epi thelial cells by converting HOCl/OCl- to anionic monochloramines, but that taurine dichloramines can be toxic to respiratory epithelial cell s through mechanisms that depend upon epithelial cell anion transport.