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Efficient killing of inhaled bacteria in ΔF508 mice: role of airway surface liquid composition
Journal article   Open access   Peer reviewed

Efficient killing of inhaled bacteria in ΔF508 mice: role of airway surface liquid composition

Paul B McCray, Joseph Zabner, Hong Peng Jia, Michael J Welsh and Peter S Thorne
American journal of physiology. Lung cellular and molecular physiology, Vol.277(1), pp.L183-L190
07/01/1999
DOI: 10.1152/ajplung.1999.277.1.L183
PMID: 10409246
url
https://doi.org/10.1152/ajplung.1999.277.1.L183View
Published (Version of record) Open Access

Abstract

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 ΔF508 cystic fibrosis transmembrane conductance regulator mutation. Naive ΔF508 −/− 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 β-defensins are salt-sensitive epithelial products, we looked for pulmonary β-defensin expression. A mouse homolog of human β-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 ΔF508 −/− mice. The estimated ASL volume was similar for both groups. There were no differences in ASL [Cl−] in ΔF508 −/− 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.

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