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Regulation of ion transporters and airway surface dynamics by lipoxin in cystic fibrosis bronchial epithelium
Author(s) -
Harvey Brian Joseph,
AlAlawi Mazen,
Verriere Valia,
Urbach Valerie
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1038.9
Subject(s) - mucociliary clearance , cystic fibrosis , lipoxin , respiratory epithelium , bumetanide , chemistry , amiloride , ion transporter , secretion , cystic fibrosis transmembrane conductance regulator , extracellular , receptor , endocrinology , medicine , biophysics , respiratory system , biochemistry , biology , lung , sodium , organic chemistry , membrane
We have investigated the role of the endogenous anti‐inflammatory lipoxin LXA 4 in modulating Cl − secretion and Na + absorption, airway surface liquid height (ASLh) and ciliary beat frequency (CBF) in CF and non‐CF bronchial epithelia. 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. LXA 4 (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 LXA 4 on ASLh was sustained over 24 hours in the CF epithelia and was inhibited by the following pre‐treatments: bumetanide, amiloride, Boc‐2 (LXA 4 receptor antagonist), reactive blue (P2Y receptor antagonist) and extracellular hexokinase (ATP hydrolysis). LXA 4 stimulated CBF, intracellular Ca 2+ mobilization, Cl − secretion and inhibited Na + absorption in the CF epithelia. 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.