Journal article
Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia
Nature (London), Vol.567(7748), pp.405-408
03/2019
DOI: 10.1038/s41586-019-1018-5
PMCID: PMC6492938
PMID: 30867598
Abstract
Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO
and Cl
secretion, reduce airway surface liquid pH, and impair respiratory host defences in people with cystic fibrosis
. Here we report that apical addition of amphotericin B, a small molecule that forms unselective ion channels, restored HCO
secretion and increased airway surface liquid pH in cultured airway epithelia from people with cystic fibrosis. These effects required the basolateral Na
, K
-ATPase, indicating that apical amphotericin B channels functionally interfaced with this driver of anion secretion. Amphotericin B also restored airway surface liquid pH, viscosity, and antibacterial activity in primary cultures of airway epithelia from people with cystic fibrosis caused by different mutations, including ones that do not yield CFTR, and increased airway surface liquid pH in CFTR-null pigs in vivo. Thus, unselective small-molecule ion channels can restore host defences in cystic fibrosis airway epithelia via a mechanism that is independent of CFTR and is therefore independent of genotype.
Details
- Title: Subtitle
- Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia
- Creators
- Katrina A Muraglia - University of Illinois Urbana-ChampaignRajeev S Chorghade - University of Illinois Urbana-ChampaignBo Ram Kim - Roy J. and Lucille A. Carver College of MedicineXiao Xiao Tang - University of IowaViral S Shah - Roy J. and Lucille A. Carver College of MedicineAnthony S Grillo - University of Illinois Urbana-ChampaignPage N Daniels - University of Illinois Urbana-ChampaignAlexander G Cioffi - University of Illinois Urbana-ChampaignPhilip H Karp - University of IowaLingyang Zhu - University of Illinois Urbana-ChampaignMichael J Welsh - University of IowaMartin D Burke - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.567(7748), pp.405-408
- DOI
- 10.1038/s41586-019-1018-5
- PMID
- 30867598
- PMCID
- PMC6492938
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- R35 GM118185 / NIGMS NIH HHS P01 HL091842 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS T32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984259444302771
Metrics
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