Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid

The link between the genetic defect in cystic fibrosis (CF) and the recentl y described breach in pulmonary host defense has focused on the role of sal t and water metabolism in the airways. Using a human bronchial xenograft mo del we demonstrate a salt-independent abnormality in bacterial killing in C F airway surface fluid (ASF). Biochemical characterization implicates the a bsence or dysfunction of a molecule critical to the constitution of normal bacterial killing. Our study suggests that CF transmembrane conductance reg ulator (CFTR) deficiency causes a primary abnormality in the composition of ASF that leads to a salt-independent defect in host defense. Importantly, this defect is corrected by adenovirus-mediated gene transfer of CFTR.