ALTERATION OF SULFATION OF GLYCOCONJUGATES, BUT NOT SULFATE TRANSPORTAND INTRACELLULAR INORGANIC SULFATE CONTENT IN CYSTIC-FIBROSIS AIRWAYEPITHELIAL-CELLS

The secreted and cell surface high molecular weight glycoconjugates (H MG) generated by primary cultures of airway epithelial cells from cyst ic fibrosis (CF) patients are oversulfated. To determine whether this abnormality is maintained in transformed CF airway epithelial cells an d whether differences in transport or intracellular accumulation of su lfate can explain this alteration, we assessed sulfate metabolism in p aired CF and normal cell lines as well as primary cultures of CF and n ormal cells. Both -acetamido-4'-isothiocyanostilbene-2,2'-disulfonic a cid-inhibitable and -resistant [S-35]sulfate efflux and influx were id entical for each pair of CF and normal cell lines. Furthermore, cell c ontent of inorganic sulfate was not significantly different in CF and normal cells. However, compared with primary CF cells that oversulfate HMG transformed CF cells oversulfated cell surface HMG but not HMG re leased into culture medium. Our results suggest that plasma membrane s ulfate transport is not altered in CF airway epithelial cells and the abnormal sulfation of HMG may be due to perturbation in intracellular sulfate activation or transfer of activated sulfate to HMG. The relati onship of this abnormality to CF transmembrane conductance regulator m utations remains to be determined.