Skip to Main content Skip to Navigation
Journal articles

Salmeterol restores secretory functions in cystic fibrosis airway submucosal gland serous cells.

Abstract : The activity of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) can be mediated by surface G protein-coupled receptors such as the beta(2)-adrenergic receptor. In this study, we explored the effect of a long-acting beta(2)-adrenergic agonist, salmeterol, on the CFTR-dependent secretory capacity of a human CF tracheal gland serous cell line (CF-KM4), homozygous for the delF508 mutation. We showed that, compared with the untreated CF serous cells, a 24-hour pre-incubation period with 200 nM salmeterol induced an 83% increase in delF508-CFTR-mediated chloride efflux. The restoration of the bioelectric properties is associated with increased apical surface pool of delF508-CFTR. Salmeterol induced a decrease in ion concentration and an increase in the level of hydration of the mucus packaged inside the CF secretory granules. The effects of salmeterol are not associated with a persistent production of cAMP. Western blotting on isolated secretory granules demonstrated immunoreactivity for CFTR and lysozyme. In parallel, we measured by atomic force microscopy an increased size of secretory granules isolated from CF serous cells compared with non-CF serous cells (MM39 cell line) and showed that salmeterol was able to restore a CF cell granule size similar to that of non-CF cells. To demonstrate that the salmeterol effect was a CFTR-dependent mechanism, we showed that the incubation of salmeterol-treated CF serous cells with CFTR-inh172 suppressed the restoration of normal secretory functions. The capacity of salmeterol to restore the secretory capacity of glandular serous cells suggests that it could also improve the airway mucociliary clearance in patients with CF.
Complete list of metadatas

Cited literature [46 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00336161
Contributor : Jean-Marie Zahm <>
Submitted on : Monday, November 3, 2008 - 9:03:15 AM
Last modification on : Thursday, July 12, 2018 - 3:56:10 PM
Long-term archiving on: : Saturday, November 26, 2016 - 1:53:11 AM

File

2008-0037OCv1.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Franck Delavoie, Michael Molinari, Magali Milliot, Jean-Marie Zahm, Christelle Coraux, et al.. Salmeterol restores secretory functions in cystic fibrosis airway submucosal gland serous cells.. American Journal of Respiratory Cell and Molecular Biology, American Thoracic Society, 2009, 40 (4), pp.388-97. ⟨10.1165/rcmb.2008-0037OC⟩. ⟨inserm-00336161⟩

Share

Metrics

Record views

206

Files downloads

241