Abnormal glutathione transport in cystic fibrosis airway epithelia

Glutathione (GSH) is a potentially important component of antioxidant defen se in the epithelial lung lining fluid. Cystic fibrosis (CF) patients have chronic inflammation in which oxidative stress can be a factor. To examine the hypothesis that the transport of GSH content was defective in CF patien ts, intracellular and extracellular GSH were measured by HPLC. Four cell li nes were used: CFT1 cells [with defective CF transmembrane conductance regu lator (CFTR), Delta F508 homozygous, two clones] and one of the CFT1 clones transfected with either normal CFTR (CFTR repleted) or beta-galactosidase. GSH content in the apical fluid was 55% lower in CFTR-deficient cultures t han in CFTR-repleted cells (P < 0.001). In contrast, intracellular GSH cont ent was similar in CFT1 cells and CFTR-repleted cells. gamma-Glutamyl trans peptidase activity, which degrades extracellular GSH, did not account for d ifferences in apical GSH. Rather, GSH efflux of CFTR-deficient cells was lo wer than that of CFTR-repleted cells. These studies suggested that decrease d GSH content in the apical fluid in CF resulted from abnormal GSH transpor t associated with a defective CFTR.