Figure 1

Consequences of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction on epithelial ion transport, airway surface hydration, mucociliary clearance and antibacterial host defence in cystic fibrosis (CF) airways. a) In normal airway epithelia, CFTR is expressed in the apical cell membrane where it functions as an anion channel that mediates secretion of Cl-/HCO3- and fluid, and controls the absorption of Na+ and fluid mediated by the amiloride-sensitive epithelial Na+ channel (ENaC). Coordinated secretion and absorption of salt and water is essential for proper hydration of airway surfaces (periciliary layer and overlying mucus gel) and normal mucus clearance. b) In CF airway epithelia, CFTR dysfunction due to various molecular mechanisms, including deficient synthesis, processing, gating, conductance or reduced stability of CFTR anion channels, causes dehydration of the periciliary and mucus layers leading to impaired mucus transport and airway mucus obstruction (dark blue area). c) Static, dehydrated mucus triggers airway inflammation and forms a nidus for bacterial infection. Once neutrophilic inflammation is established, the release of proteases, such as neutrophil elastase, augments ENaC activity by proteolytic cleavage and further aggravates airway surface dehydration and mucociliary dysfunction. d) Lack of CFTR-mediated HCO3- secretion causes reduced airway surface liquid pH (yellow area), which renders antimicrobial peptides such as lysozyme and lactoferrin less effective and contributes to impaired defence against bacterial infection in CF airways.