CYSTIC-FIBROSIS EPITHELIAL-CELLS HAVE A RECEPTOR FOR PATHOGENIC BACTERIA ON THEIR APICAL SURFACE

Chronic colonization and infection of the lung with Pseudomonas aerugi nosa is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. We found that polarized CF bronchial and pancreatic epi thelia bound P. aeruginosa in a reversible and dose-dependent manner. There was significantly greater binding to CF bronchial and pancreatic cells than to their matched pairs rescued with the wild-type CF trans membrane conductance regulator. Bound P. aeruginosa were easily displa ced by unlabeled P. aeruginosa but not by Escherichia coli, an organis m that does not cause significant pulmonary disease in CF. In contrast , Staphylococcus aureus, a frequent pathogen in CF, could effectively displace bound P. aeruginosa from its receptor. We found undersialylat ion of apical proteins and a higher concentration of asialoganglioside 1 (aGM(1)) in apical membranes of CF compared with rescued epithelia. Incubation of P. aeruginosa with aGM(1) reduced its binding, as did t reatment of the epithelia with the tetrasaccharide moiety of this gang lioside (Gal(beta 1-3)GalNAc(beta 1-4)Gal(beta 1-4)Glc). Finally, an a ntibody to aGM(1) effectively displaced P. aeruginosa from its binding site and blocked binding of S. aureus to CF cells but not to rescued cells. These results show that the tetrasaccharide of aGM(1) is a rece ptor for P. aeruginosa and S. aureus and that its increased abundance in the apical membrane of CF epithelia makes it a likely contributor t o the pathogenesis of bacterial infections in the CF lung.