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

Artikel i vetenskaplig tidskrift
Författare Anna Ermund
Lauren N Meiss
Jenny K Gustafsson
Gunnar C. Hansson
Publicerad i European Journal of Pharmacology
Volym 764
Sidor 109-117
ISSN 0014-2999
Publiceringsår 2015
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 109-117
Språk en
Länkar dx.doi.org/10.1016/j.ejphar.2015.06...
Ämnesord 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
Ämneskategorier Farmakologi

Sammanfattning

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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