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Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus

Journal article
Authors Anna Ermund
Lauren N Meiss
Jenny K Gustafsson
Gunnar C. Hansson
Published in European Journal of Pharmacology
Volume 764
Pages 109-117
ISSN 0014-2999
Publication year 2015
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 109-117
Language en
Links dx.doi.org/10.1016/j.ejphar.2015.06...
Keywords Calcium chelator, Hyperosmolarity, Mouse ileum, Mucus attachment, Osmolyte, FUNCTIONAL CFTR CHANNEL, DRY-POWDER MANNITOL, MUCOCILIARY CLEARANCE, AIRWAY INFLAMMATION, MUCIN, DYSFUNCTION, MECHANISMS, INHALATION, SECRETION, RELEASE, Pharmacology & Pharmacy
Subject categories Pharmacology

Abstract

A non-functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) leads to the disease cystic fibrosis (CF). Although the CFTR is expressed in multiple organs, pulmonary disease is the major cause of illness and death in patients with CF. Stagnant mucus, causing airway obstruction, bacterial overgrowth, persistent inflammation and tissue destruction characterizes the disease, but how the defect in CFTR function is coupled to the mucus phenotype is still controversial. We have recently shown that bicarbonate ions passing through CFTR are necessary for proper unfolding of the MUC2 mucin, thus highlighting the importance of bicarbonate ion transport via the CFTR and the ability of these ions to raise the pH and chelate calcium bound to the mucin as the important steps in forming normal mucus. In order to find potential CF treatments and expand our knowledge about the usefulness of bicarbonate as an active ingredient in formulations to alleviate mucus plugging, we used an Ussing-type chamber and explants from the F508del-CFTR mutant mouse ileum to test the effect of calcium chelators on mucus attachment, either in isolation or in combination with osmolytes such as mannitol or hypertonic saline. We found that increasing the concentration of bicarbonate, both alone or in combination with increased osmolarity of the solution, detached the otherwise attached CF mucus. (C) 2015 Elsevier B.V. All rights reserved.

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