Journal article
V-type ATPase Mediates Airway Surface Liquid Acidification in Pig Small Airway Epithelial Cells
American journal of respiratory cell and molecular biology, Vol.65(2), pp.146-156
03/31/2021
DOI: 10.1165/rcmb.2020-0349OC
PMCID: PMC8399571
PMID: 33789071
Abstract
In a new born pig cystic fibrosis (CF) model, the ability of gland-containing airways to fight infection was affected by at least two major host-defense defects: impaired mucociliary transport and a lower airway-surface liquid (ASL) pH. In the gland-containing airways, ASL pH is balanced by CFTR and ATP12A, which respectively control HCO3- transport and proton secretion. We found that, although porcine small airway tissue expressed little ATP12A, the ASL of epithelial cultures from CF distal small airways (diameter <200 μm) were nevertheless more acidic (compared to non-CF). Therefore, we hypothesized that gland-containing airways vs. small airways control acidification using distinct mechanisms. Our microarray data suggested that small airway epithelia mediate proton secretion via ATP6V0D2, an isoform of the V0d subunit of the H+-translocating plasma membrane V-type ATPase. Immunofluorescence of small airways verified the expression of the V0d2 subunit isoform at the apical surface of Muc5B+ secretory cells, but not ciliated cells. Inhibiting the V-type ATPase with bafilomycin A1 elevated the ASL pH of small airway cultures, in the presence or absence of HCO3-, and decreased ASL viscosity. These data suggest that, unlike large airways, which are acidified by ATP12A activity, small airways are acidified by V-type ATPase, thus identifying V-type ATPase as a novel therapeutic target for small airways diseases.
Details
- Title: Subtitle
- V-type ATPase Mediates Airway Surface Liquid Acidification in Pig Small Airway Epithelial Cells
- Creators
- Xiaopeng Li - Michigan State UniversityRaul Villacreses - University of IowaIan M Thornell - University of IowaJulio Noriega - University of IowaSteven Mather - University of IowaChristian M Brommel - University of IowaLin Lu - University of IowaAdam Zabner - University of IowaAnnie Ehler - University of IowaDavid K Meyerholz - University of IowaDavid A Stoltz - University of IowaJoseph Zabner - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.65(2), pp.146-156
- DOI
- 10.1165/rcmb.2020-0349OC
- PMID
- 33789071
- PMCID
- PMC8399571
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Grant note
- P01 HL091842 / NHLBI NIH HHS
- Language
- English
- Date published
- 03/31/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Pathology; Internal Medicine
- Record Identifier
- 9984186533202771
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