The Relationship of Chronic Mucin Secretion to Airway Disease in Normal and CFTR-Deficient Mice

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Abstract
In the cystic fibrosis (CF) patient, lung function decreases throughout life as a result of continuous cycles of infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus . The mechanism un- derlying the pathophysiology of the disease in humans has not been established. However, it has been sug- gested that abnormal, tenacious mucus, resulting perhaps from improper hydration from loss of Cl 2 secre- tion via the cystic fibrosis transmembrane conductance regulator (CFTR) protein, impairs clearance of bacteria from the CF airway and provides an environment favorable to bacterial growth. If this hypothesis is correct, it could explain the absence of respiratory disease in CFTR-deficient mice, since mice have only a single submucosal gland and display few goblet cells in their lower airways, even when exposed to bac- teria. To test this hypothesis further, we induced allergic airway disease in CFTR-deficient mice. We found that induction of allergic airway disease in mice, unlike bacterial infection, results in an inflamma- tory response characterized by goblet cell hyperplasia, increased mucin gene expression, and increased production of mucus. However, we also found that disease progression and resolution is identical in Cftr 2 / 2 mice and control animals. Furthermore, we show that the presence of mucus in the Cftr 2 / 2 airway does not