Salmeterol restores secretory functions in cystic fibrosis airway submucosal gland serous cells
| Autor: | Magali Milliot, Gérard Balossier, Franck Delavoie, Christelle Coraux, Jean-Marie Zahm, Michael Molinari, Jean Michel |
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| Přispěvatelé: | Interface biomatériaux/Tissus hôtes, Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Reims Champagne-Ardenne (URCA), Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Reims Champagne-Ardenne (URCA), GlaxoSmithKline, Association Vaincre la Mucoviscidose, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Zahm, Jean-Marie |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cystic Fibrosis
submucosal gland serous cell MESH: Secretory Vesicles Clinical Biochemistry Intracellular Space Cystic Fibrosis Transmembrane Conductance Regulator Cystic fibrosis [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract 0302 clinical medicine Serous Membrane Cyclic AMP MESH: Electrophysiological Phenomena CFTR Receptor Salmeterol Xinafoate MESH: Cyclic AMP MESH: Cystic Fibrosis Transmembrane Conductance Regulator 0303 health sciences MESH: Exocytosis biology Chemistry Serous membrane Cell Polarity respiratory system Secretory Vesicle Cystic fibrosis transmembrane conductance regulator 3. Good health Trachea Serous fluid medicine.anatomical_structure MESH: Epithelial Cells MESH: Intracellular Space MESH: Cell Polarity MESH: Forskolin Pulmonary and Respiratory Medicine medicine.medical_specialty MESH: Ions MESH: Cystic Fibrosis Mucociliary clearance salmeterol MESH: Serous Membrane Exocytosis Article Cell Line 03 medical and health sciences Chlorides Internal medicine medicine Humans Albuterol MESH: Chlorides Molecular Biology 030304 developmental biology Ions MESH: Humans Secretory Vesicles MESH: Albuterol Colforsin Epithelial Cells Cell Biology medicine.disease Mucus Electrophysiological Phenomena respiratory tract diseases MESH: Cell Line Endocrinology 030228 respiratory system MESH: Muramidase biology.protein [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract Muramidase secretory granule MESH: Trachea |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology American Journal of Respiratory Cell and Molecular Biology, American Thoracic Society, 2009, 40 (4), pp.388-97. ⟨10.1165/rcmb.2008-0037OC⟩ American Journal of Respiratory Cell and Molecular Biology, 2009, 40 (4), pp.388-97. ⟨10.1165/rcmb.2008-0037OC⟩ |
| ISSN: | 1044-1549 1535-4989 |
| DOI: | 10.1165/rcmb.2008-0037OC⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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