Acidic pH increases airway surface liquid viscosity in cystic fibrosis

The Journal of Clinical Investigation
Xiao Xiao TangMichael J Welsh

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 HCO3- 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 AS...Continue Reading

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Citations

Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Viral S ShahMichael J Welsh
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Methods Mentioned

BETA
glycosylation
shear rheometry
confocal microscopy
in
sedation
PCR

Software Mentioned

GraphPad
GraphPad Prism

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