Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells

Journal Article · Sat Oct 01 00:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.06.010· OSTI ID:20717660

Baconnais, S; Delavoie, F ^[1]; Zahm, J M; Milliot, M; Castillon, N ^[2]; Terryn, C ^[1]; Banchet, V ^[1]; Michel, J ^[1]; Danos, O ^[3]; Merten, M ^[4]; Chinet, T ^[5]; Zierold, K ^[6]; Bonnet, N ^[2]; Balossier, G ^[1]

---

1. INSERM ERM 203, Laboratoire de Microscopie Electronique Analytique, IFR53, Universite de Reims Champagne-Ardenne, 21 rue Clement Ader, 51685 Reims Cedex 2 (France)
2. INSERM UMRS 514, IFR 53, CHU Maison Blanche, 45, rue Cognac-Jay, 51092 Reims Cedex (France)
3. Genethon, CNRS UMR 8115, 1bis rue de l'Internationale, Evry (France)
4. INSERM EMI 0014, Faculte de Medecine, 9, Avenue de la Foret de Haye, BP 184, 54505 Vandoeuvre Les Nancy cedex, (France)
5. Laboratoire de Biologie et Pharmacologie des Epitheliums Respiratoires, UFR Paris Ile de France Ouest, Boulogne-Billancourt (France)
6. Max Planck Institute of Molekular Physiology, Laboratory for Analytical Microscopy, Otto-Hahn-Strasse 11, D-44227 Dortmund (Germany)

The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na{sup +} absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na{sup +}, Mg{sup 2+}, P, S and Cl{sup -}) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR{sub inh}-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.

• OSTI ID: 20717660
• Journal Information: Experimental Cell Research, Vol. 309, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2005.06.010; PII: S0014-4827(05)00286-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHLORINE IONS
DEHYDRATION
ELECTRON PROBES
EXPANSION
FIBROSIS
GLANDS
HYDRATION
INDIUM IONS
MAGNESIUM IONS
MICROANALYSIS
MICROSCOPY
X RADIATION