Submucosal glands and airway defense
Abstract
Most airway mucus is produced by submucosal glands in response to neural signals. Gland mucus traps microbes, inhibits their replication, and clears them from the airways. In cystic fibrosis mucus clearance is compromised, allowing pathogens to persist in static mucus. These trigger an influx of inflammatory cells, but optimal effectiveness of inflammation, and especially its resolution, also requires effective mucus clearance. Our objective is to understand the basis for defective mucus clearance in cystic fibrosis. We discovered that in subjects with cystic fibrosis, submucosal gland secretion in response to agents that elevate intracellular cyclic AMP level is completely lost and mucus stimulated by elevating intracellular Ca2+ level is thicker. We hypothesize that loss of functional cystic fibrosis transmembrane conductance regulator from gland serous cells renders them unable to secrete anions and fluid in response to any stimulus, resulting in thickened gland mucus that can be tethered to the gland ducts. In primary ciliary dyskinesias, mucus is normal, but the dysfunctional cilia lining the gland ducts may also lead to inadequate clearance of mucus from glands. Thus, understanding of lung pathology in each disease may require that an improved understanding of gland structure and function be added to our rapidly growing understanding of surface epithelia.
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Viral-mediated injury to these cells and to the epithelium lining large airways and ciliated ducts contributes to the evolution of influenza-associated bacterial pneumonia by compromising the mucus stream and hindering mucociliary clearance of bacteria from the respiratory tract.
“Viral-mediated injury to these cells and to the epithelium lining large airways and ciliated ducts undoubtedly contributes to the evolution of influenza-associated bacterial pneumonia by compromising the mucus stream and hindering mucociliary clearance of bacteria from the respiratory tract”
From Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection (2012) · cites this paper as [48]
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Paddock, C. D., Liu, L., Denison, A. M., Bartlett, J. H., Holman, R. C., DeLeon-Carnes, M., Emery, S. L., Drew, C. P., Shieh, W.-J., Uyeki, T. M., et al. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir861 · Cited by 171 · see citing works
- Authors
- Wine, J. J., & Joo, N. S.
- Affiliations
- Stanford University (US)
- Corresponding author
- Wine, Jeffrey J.
- Venue
- Proceedings of the American Thoracic Society
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-01
- Volume
- 1
- Issue
- 1
- Pages
- 47-53
- ISSN
- 1546-3222 (ISSN-L)
- 1943-5665
- OpenAlex
- W2131145961
- Cited by
- 223
- References
- 61
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 15 · 2019: 5 · 2018: 8 · 2017: 6 · 2016: 17 · 2015: 21 · 2014: 18 · 2013: 11 · 2012: 20
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proceedings of the American Thoracic Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50hl060288-02)
- National Heart, Lung, and Blood Institute (HL-60288)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 51817, R01DK051817)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- submucosal glands, airway mucus, mucus clearance, cystic fibrosis, primary ciliary dyskinesia, CFTR, cyclic AMP, intracellular calcium, mucus viscosity, airway defense, serous cells, inflammation resolution
- MeSH terms
- Animals, Cystic Fibrosis, Exocrine Glands, Humans, Mucus, Respiratory Mucosa
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