Journal article
Acidic pH increases airway surface liquid viscosity in cystic fibrosis
The Journal of clinical investigation, Vol.126(3), pp.879-891
03/01/2016
DOI: 10.1172/JCI83922
PMCID: PMC4767348
PMID: 26808501
Abstract
Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO
3
–
concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca
2+
concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca
2+
concentration, and/or altering electrostatic interactions in ASL might benefit early CF.
Details
- Title: Subtitle
- Acidic pH increases airway surface liquid viscosity in cystic fibrosis
- Creators
- Xiao Xiao Tang - Department of Internal MedicineLynda S Ostedgaard - Department of Internal MedicineMark J Hoegger - Department of Internal MedicineThomas O Moninger - Central Microscopy Research Facilities, University of Iowa, Iowa City, Iowa, USAPhilip H Karp - Department of Internal MedicineJames D McMenimen - Department of Internal MedicineBiswa Choudhury - Glycobiology Research and Training Center andAjit Varki - Glycobiology Research and Training Center andDavid A Stoltz - Department of Internal MedicineMichael J Welsh - Department of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.126(3), pp.879-891
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI83922
- PMID
- 26808501
- PMCID
- PMC4767348
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 03/01/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984025455802771
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