Abstract
Aims: We have investigated the role of the endogenous anti-inflammatory lipoxin LXA4 in modulating Cl- secretion and Na+ absorption, airway surface liquid height (ASLh) and ciliary beat frequency (CBF) in CF and non-CF bronchial epithelia.
Methods: CF (CuFi-1) and non-CF (NuLi-1) bronchial epithelial cell lines were grown under an air-surface liquid interface into well-differentiated epithelia. ASLh and CBF were measured using confocal fluorescence microscopy and ion transport using patch-clamp and short-circuit current techniques.
Results: LXA4 (1nM) treatment for 15 minutes, increased ASLh by 47.5±0.5% and 103.0±3.0% in NuLi and CuFi epithelia respectively (P<0.001, n=18). The stimulatory effect of LXA4 on ASLh was sustained over 24 hours in the CF epithelia and was inhibited by the following pre-treatments: bumetanide, amiloride, Boc-2 (LXA4 receptor antagonist), reactive blue (P2Y receptor antagonist) and extracellular hexokinase (ATP hydrolysis). LXA4 stimulated CBF, intracellular Ca2+ mobilization, Cl- secretion and inhibited Na+ absorption in the CF epithelia.
Conclusions: These effects of lipoxin involving the FPR2 receptor, apical ATP release, purinoreceptor activation, inhibition of Na+ absorption and stimulation of Cl- secretion to enhance airway surface liquid dynamics open up a new therapeutic avenue to promote mucociliary clearance in cystic fibrosis airways.
- © 2011 ERS