Journal article
Paracellular bicarbonate flux across human cystic fibrosis airway epithelia tempers changes in airway surface liquid pH
The Journal of physiology, Vol.598(19), pp.4307-4320
10/01/2020
DOI: 10.1113/JP280120
PMCID: PMC7589346
PMID: 32627187
Abstract
Key points
Cl(-)and HCO(3)(-)had similar paracellular permeabilities in human airway epithelia. P-Cl/P(Na)of airway epithelia was unaltered by pH 7.4 vs. pH 6.0 solutions. Under basal conditions, calculated paracellular HCO(3)(-)flux was secretory. Cytokines that increased airway surface liquid pH decreased or reversed paracellular HCO(3)(-)flux. HCO(3)(-)flux through the paracellular pathway may counterbalance effects of cellular H(+)and HCO(3)(-)secretion. Airway epithelia control the pH of airway surface liquid (ASL), thereby optimizing respiratory defences. Active H(+)and HCO(3)(-)secretion by airway epithelial cells produce an ASL that is acidic compared with the interstitial space. The paracellular pathway could provide a route for passive HCO(3)(-)flux that also modifies ASL pH. However, there is limited information about paracellular HCO(3)(-)flux, and it remains uncertain whether an acidic pH produced by loss of cystic fibrosis transmembrane conductance regulator anion channels or proinflammatory cytokines might alter the paracellular pathway function. To investigate paracellular HCO(3)(-)transport, we studied differentiated primary cultures of human cystic fibrosis (CF) and non-CF airway epithelia. The paracellular pathway was pH-insensitive at pH 6.0vs. pH 7.4 and was equally permeable to Cl(-)and HCO3-. Under basal conditions at pH similar to 6.6, calculated paracellular HCO(3)(-)flux was weakly secretory. Treating epithelia with IL-17 plus TNF alpha alkalinized ASL pH to similar to 7.0, increased paracellular HCO(3)(-)permeability, and paracellular HCO(3)(-)flux was negligible. Applying IL-13 increased ASL pH to similar to 7.4 without altering paracellular HCO(3)(-)permeability, and calculated paracellular HCO(3)(-)flux was absorptive. These results suggest that HCO(3)(-)flux through the paracellular pathway counterbalances, in part, changes in the ASL pH produced via cellular mechanisms. As the pH of ASL increases towards that of basolateral liquid, paracellular HCO(3)(-)flux becomes absorptive, tempering the alkaline pH generated by transcellular HCO(3)(-)secretion.
Details
- Title: Subtitle
- Paracellular bicarbonate flux across human cystic fibrosis airway epithelia tempers changes in airway surface liquid pH
- Creators
- Ian M. Thornell - Roy J. and Lucille A. Carver College of MedicineTayyab Rehman - Roy J. and Lucille A. Carver College of MedicineAlejandro A. Pezzulo - Roy J. and Lucille A. Carver College of MedicineMichael J. Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.598(19), pp.4307-4320
- DOI
- 10.1113/JP280120
- PMID
- 32627187
- PMCID
- PMC7589346
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- HL007638; HL140261; HL051670; HL091842 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Cystic Fibrosis Foundation Research Development Program pilot award Gilead Sciences Research Program in Cystic Fibrosis Parker B. Francis Fellowship Program
- Language
- English
- Date published
- 10/01/2020
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984259508402771
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