Efficient killing of inhaled bacteria in DeltaF508 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 mucosal defenses and airway surface liquid (ASL) Cl(-) were altered by the DeltaF508 cystic fibrosis transmembrane conductance regulator mutation. Naive DeltaF508 -/- and +/- mice showed no pulmonary inflammation and after inhaled Pseudomonas aeruginosa had similar inflammatory responses and bacterial clearance rates. We therefore investigated components of the innate immune system. 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 identified; the mRNA was expressed in the lung. Using a radiotracer technique, ASL volume and Cl(-) concentration ([Cl(-)]) were measured in cultured tracheal epithelia from normal and DeltaF508 -/- mice. The estimated ASL volume was similar for both groups. There were no differences in ASL [Cl(-)] in DeltaF508 -/- 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 factors, including MBD-1, may be normally active.
Departments of Pediatrics, Internal Medicine, and Occupational and Environmental Health, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. paul-mccray@uiowa.edu
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McCray
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Zabner
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Welsh
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Thorne
D000280:Administration, Inhalation; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000037:antagonists & inhibitors; D001424:Bacterial Infections / Q000517:prevention & control*; D018407:Bacterial Physiological Phenomena; D001483:Base Sequence / Q000235:genetics; D001826:Body Fluids / Q000502:physiology; D001980:Bronchi / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D008171:Lung Diseases / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D023083:beta-Defensins
D000900:Anti-Bacterial Agents; C120555:Defb1 protein, mouse; D011506:Proteins; D023083:beta-Defensins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride