Am. J. Respir. Cell Mol. Biol., Volume 25, Number 1, July, 2001 21-25

Salt-Independent Abnormality of Antimicrobial Activity in Cystic Fibrosis Airway Surface Fluid

Robert Bals, Daniel J. Weiner, Rupalie L. Meegalla, Frank Accurso, and James M. Wilson

Institute for Human Gene Therapy, Departments of Medicine and Molecular and Cellular Engineering, University of Pennsylvania; The Wistar Institute; Division of Pulmonary Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and The Children's Hospital and the University of Colorado School of Medicine, Denver, Colorado

The link between the genetic defect in cystic fibrosis (CF) and the recently described breach in pulmonary host defense has focused on the role of salt and water metabolism in the airways. Using a human bronchial xenograft model we demonstrate a salt-independent abnormality in bacterial killing in CF airway surface fluid (ASF). Biochemical characterization implicates the absence or dysfunction of a molecule critical to the constitution of normal bacterial killing. Our study suggests that CF transmembrane conductance regulator (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.

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