The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure
Open accessAbstract
The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients likely involves poor mucus clearance. A recent model of mucus clearance predicts that mucus flow depends on the relative mucin concentration of the mucus layer compared with that of the periciliary layer; however, mucin concentrations have been difficult to measure in CF secretions. Here, we have shown that the concentration of mucin in CF sputum is low when measured by immunologically based techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage at antibody recognition sites. Using physical size exclusion chromatography/differential refractometry (SEC/dRI) techniques, we determined that mucin concentrations in CF secretions were higher than those in normal secretions. Measurements of partial osmotic pressures revealed that the partial osmotic pressure of CF sputum and the retained mucus in excised CF lungs were substantially greater than the partial osmotic pressure of normal secretions. Our data reveal that mucin concentration cannot be accurately measured immunologically in proteolytically active CF secretions; mucins are hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict mucus layer-dependent osmotic compression of the periciliary liquid layer in CF lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which contributes to key infectious and inflammatory components of CF lung disease.
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Cites
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Self-citationCystic Fibrosis Airway Epithelia Fail to Kill Bacteria Because of Abnormal Airway Surface Fluid
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A Periciliary Brush Promotes the Lung Health by Separating the Mucus Layer from Airway Epithelia
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Self-citationReduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung
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Risk Factors for Bronchiectasis in Children with Cystic Fibrosis
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Cited by
Elborn, J. S. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00576-6 · Cited by 1,805
Respiratory epithelial cells orchestrate pulmonary innate immunity
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Physicochemical properties of mucus and their impact on transmucosal drug delivery
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The innate immune function of airway epithelial cells in inflammatory lung disease
Hiemstra, P. S., McCray, P. B., & Bals, R. (2015) · European Respiratory Journal · doi:10.1183/09031936.00141514 · Cited by 422
Muco-Obstructive Lung Diseases
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Metadata
- Authors
- Henderson, A. G., Ehre, C., Button, B., Abdullah, L. H., Cai, L.-H., Leigh, M. W., DeMaria, G. C., Matsui, H., Donaldson, S. H., Davis, C. W., Sheehan, J. K., Boucher, R. C., & Kesimer, M.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-06-02
- Volume
- 124
- Issue
- 7
- Pages
- 3047-3060
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2147868143
- Cited by
- 326
- References
- 42
- FWCI
- 17.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Henderson, A. G., Ehre, C., Button, B., Abdullah, L. H., Cai, L.-H., Leigh, M. W., DeMaria, G. C., Matsui, H., Donaldson, S. H., Davis, C. W., Sheehan, J. K., Boucher, R. C., & Kesimer, M. (2014). Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure. Journal of Clinical Investigation. https://doi.org/10.1172/jci73469
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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