title: Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid.
abstract: 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.
authors.affiliation: Institute for Human Gene Therapy, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bals
authors.forename: D J
authors.initials: DJ
authors.lastname: Weiner
authors.forename: R L
authors.initials: RL
authors.lastname: Meegalla
authors.forename: F
authors.initials: F
authors.lastname: Accurso
authors.forename: J M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D012965:Sodium Chloride / Q000378:metabolism*; D014183:Transplantation, Heterologous; D023083:beta-Defensins / Q000276:immunology / Q000502:physiology*
chemical_list: D000906:Antibodies; C505032:CFTR protein, human; D023083:beta-Defensins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride