Efficient killing of inhaled bacteria in Delta F508 mice: role of airway surface liquid composition

Cystic fibrosis mice have been generated by gene targeting but show little lung disease without repeated exposure to bacteria. We asked if murine muco sal defenses and airway surface liquid (ASL) Cl- were altered by the Delta F508 cystic fibrosis transmembrane conductance regulator mutation. Naive De lta F508 -/- and +/- mice showed no pulmonary inflammation and after inhale d Pseudomonas aeruginosa had similar inflammatory responses and bacterial c learance rates. We therefore investigated components of the innate immune s ystem. Bronchoalveolar lavage fluid from mice killed Escherichia coli, and the microbicidal activity was inhibited by NaCl. Because beta-defensins are salt-sensitive epithelial products, we looked for pulmonary beta-defensin expression. A mouse homolog of human beta-defensin-1 (termed "MBD-1") was i dentified; the mRNA was expressed in the lung. Using a radiotracer techniqu e, ASL volume and Cl- concentration ([Cl-]) were measured in cultured trach eal epithelia from normal and Delta F508 -/- mice. The estimated ASL volume was similar for both groups. There were no differences in ASL [Cl-] in Del ta FS08 -/- and normal mice (13.8 +/- 2.6 vs. 17.8 +/- 5.6 meq/l). Because ASL [Cl-] is low in normal and mutant mice, salt-sensitive antimicrobial fa ctors, including MBD-1, may be normally active.