Abstract | RATIONALE: OBJECTIVES: METHODS: We used the Scnn1b-Tg mouse as a model of CF lung disease and determined effects of genetic deletion of NE (NE(-/-)) on the pulmonary phenotype. Furthermore, we used novel Foerster resonance energy transfer (FRET)-based NE reporter assays to assess NE activity in bronchoalveolar lavage from Scnn1b-Tg mice and sputum from patients with CF. MEASUREMENTS AND MAIN RESULTS: Lack of NE significantly reduced airway neutrophilia, elevated mucin expression, goblet cell metaplasia, and distal airspace enlargement, but had no effect on airway mucus plugging, bacterial infection, or pulmonary mortality in Scnn1b-Tg mice. By using FRET reporters, we show that NE activity was elevated on the surface of airway neutrophils from Scnn1b-Tg mice and patients with CF. CONCLUSIONS: Our results suggest that NE plays an important role in the in vivo pathogenesis and may serve as a therapeutic target for inflammation, mucus hypersecretion, and structural lung damage and indicate that additional rehydration strategies may be required for effective treatment of airway mucus obstruction in CF.
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Authors | Stefanie Gehrig, Julia Duerr, Michael Weitnauer, Claudius J Wagner, Simon Y Graeber, Jolanthe Schatterny, Stephanie Hirtz, Abderrazzaq Belaaouaj, Alexander H Dalpke, Carsten Schultz, Marcus A Mall |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 189
Issue 9
Pg. 1082-92
(May 01 2014)
ISSN: 1535-4970 [Electronic] United States |
PMID | 24678594
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Epithelial Sodium Channels
- Scnn1b protein, mouse
- Leukocyte Elastase
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Topics |
- Airway Obstruction
(genetics, pathology, physiopathology)
- Animals
- Bronchiectasis
(etiology)
- Cystic Fibrosis
(genetics, pathology, physiopathology)
- Disease Models, Animal
- Epithelial Sodium Channels
- Gene Deletion
- Humans
- Inflammation
(genetics, pathology, physiopathology)
- Kaplan-Meier Estimate
- Leukocyte Elastase
(genetics, physiology)
- Lung
(pathology, physiopathology)
- Mice
- Mucus
(metabolism)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Sputum
(microbiology)
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