Peer Reviewed

1

Document Type

Article

Publication Date

7-8-2014

Keywords

Cystic fibrosis, ENaC, lipoxin A4

Funder/Sponsor

INSERM the French National Institute of Health (VU), the CHU of Montpellier (VU), the French Cystic Fibrosis Association Vaincre La Mucoviscidose (VU), Molecular Medicine Ireland Clinician-Scientist Fellowship (MA), and the Higher Education Authority of Ireland and EU COST Action

Comments

The original article is available at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2051-817X

Abstract

In cystic fibrosis (CF), the airway surface liquid (ASL) is depleted. We previously demonstrated that lipoxin A4 (LXA4) can modulate ASL height (ASLh) through actions on Cl(-) transport. Here, we report novel effects of lipoxin on the epithelial Na(+) channel ENaC in this response. ASL dynamics and ion transport were studied using live-cell confocal microscopy and short-circuit current measurements in CF (CuFi-1) and non-CF (NuLi-1) cell cultures. Low physiological concentrations of LXA4 in the picomolar range produced an increase in ASLh which was dependent on inhibition of an amiloride-sensitive Na(+) current and stimulation of a bumetanide-sensitive Cl(-) current. These ion transport and ASLh responses to LXA4 were blocked by Boc-2 an inhibitor of the specific LXA4 receptor ALX/FPR2. LXA4 affected the subcellular localization of its receptor and enhanced the localization of ALX/FPR2 at the apical membrane of CF cells. Our results provide evidence for a novel effect of low physiological concentrations of LXA4 to inhibit airway epithelial Na(+) absorption that results in an ASL height increase in CF airway epithelia.

Disciplines

Medical Molecular Biology | Medical Sciences

Citation

Al-Alawi M, Buchanan P, Verriere V, Higgins G, McCabe O, Costello RW, McNally P, Urbach V, Harvey BJ. Physiological levels of lipoxin A4 inhibit ENaC and restore airway surface liquid height in cystic fibrosis bronchial epithelium. Physiological Reports. 2014 Aug 7;2(8). pii: e12093.

PubMed ID

25107986

DOI Link

10.14814/phy2.12093

Share

COinS