Evidence for Periciliary Liquid Layer Depletion, Not Abnormal Ion Composition, in the Pathogenesis of Cystic Fibrosis Airways Disease

摘要: The pathogenesis of cystic fibrosis (CF) airways infection is unknown. Two hypotheses, "hypotonic [low salt]/defensin" and "isotonic volume transport/mucus clearance," attempt to link defects in transmembrane conductance regulator-mediated ion transport CF disease. We tested these hypotheses with planar cylindrical culture models found no evidence that the liquids lining airway surfaces were hypotonic or salt concentrations differed between normal cultures. In contrast, epithelia exhibited abnormally high rates surface liquid absorption, which depleted periciliary layer abolished mucus transport. failure clear thickened from likely initiates infection. These data indicate therapy for lung disease should not be directed at modulation ionic composition, but rather restoring (salt water) on surfaces.