Terminal sialylation is altered in airway cells with impaired CFTR-mediated chloride transport

Reduced terminal sialylation at the surface of airway epithelial cells from patients with cystic fibrosis may predispose them to bacterial infection. To determine whether a lack of chloride transport or misprocessing of mutan t cystic fibrosis transmembrane conductance regulator (CFTR) is critical fo r the alterations in glycosylation, we studied a normal human tracheal epit helial cell line (9/HTEo(-)) transfected with the regulatory (R) domain of CFTR, which blocks CFTR-mediated chloride transport; Delta F508 CFTR, which is misprocessed, wild-type CFTR; or empty vector. Reduced cAMP-stimulated chloride transport is seen in the R domain and DF508 transfectants. These t wo cell lines had consistent, significantly reduced binding of elderberry b ark lectin, which recognizes terminal sialic acid in the alpha -2,6 configu ration. Binding of other lectins, including Maakia amurensis lectin, which recognizes sialic acid in the alpha -2,3 configuration, was comparable in a ll cell lines. Because the cell surface change occurred in R domain-transfe cted cells, which continue to express wild-type CFTR, it cannot be related entirely to misprocessed or overexpressed CFTR. It is associated most close ly with reduced CFTR activity.