Physiological levels of lipoxin A4 inhibit ENaC and restore airway surface liquid height in cystic fibrosis bronchial epithelium. Mazen Al-Alawi Paul Buchanan Valia Verriere Gerard Higgins Olive McCabe Richard W. Costello Paul McNally Valérie Urbach Brian J. Harvey 10779/rcsi.10787213.v1 https://repository.rcsi.com/articles/journal_contribution/Physiological_levels_of_lipoxin_A4_inhibit_ENaC_and_restore_airway_surface_liquid_height_in_cystic_fibrosis_bronchial_epithelium_/10787213 <p>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.</p> 2019-11-22 16:42:50 Cystic fibrosis ENaC lipoxin A4 Molecular Medicine