Journal
MUCOSAL IMMUNOLOGY
Volume 5, Issue 4, Pages 397-408Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2012.17
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Funding
- Clinical Proteomics Laboratory at the UNC Thurston Arthritis Research Center
- Immunotechnology Core at the UNC Center for Gastrointestinal Biology and Disease
- NIH [P30 DK34987]
- Cystic Fibrosis Foundation
- Cystic Fibrosis Research Development Program [RDP R026]
- National Institute of Health [P30 DK065988, P50 HL060280]
- [RANDEL07P0]
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It has been postulated that mucus stasis is central to the pathogenesis of obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg(+)) mice, airway-targeted overexpression of the epithelial Na+ channel beta subunit causes airway surface dehydration, which results in mucus stasis and inflammation. Bronchoalveolar lavage from neonatal Scnn1b-Tg(+) mice, but not wild-type littermates, contained increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg(+) mice lung bacterial flora included environmental and oropharyngeal species, suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of the Toll-interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg(+) mice did not modify airway mucus obstruction, but caused defective neutrophil recruitment and increased bacterial infection, which persisted into adulthood. Scnn1b-Tg(+) mice derived into germ-free conditions exhibited mucus obstruction similar to conventional Scnn1b-Tg(+) mice and sterile inflammation. Collectively, these data suggest that dehydration-induced mucus stasis promotes infection, compounds defects in other immune mechanisms, and alone is sufficient to trigger airway inflammation.
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