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The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation

Journal article
Authors Anna Ermund
Lauren N Meiss
Brendan Dolan
A. Bahr
N. Klymiuk
Gunnar C. Hansson
Published in European Respiratory Journal
Volume 52
Issue 2
ISSN 0903-1936
Publication year 2018
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Keywords functional cftr channel, mucociliary transport, mucin, disease, trachea, model
Subject categories Respiratory Medicine and Allergy


The beneficial effect of anticholinergic therapy for chronic lung diseases such as chronic obstructive pulmonary disease (COPD) is well documented, although cholinergic stimulation paradoxically inhibits liquid absorption, increases ciliary beat frequency and increases airway surface liquid transport. Using pig tracheobronchial explants, we quantified basal mucus transport before as well as after incubation with the clinically used antimuscarinic compound ipratropium bromide (Atrovent) and stimulation with acetylcholine. As expected, surface liquid transport was increased by acetylcholine and carbachol. In contrast, the mucus bundles secreted from the submucosal glands normally transported on the cilia were stopped from moving by acetylcholine, an effect inhibited by ipratropium bromide. Interestingly, in pigs lacking a functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel, the mucus bundles were almost immobile. As in wild-type pigs, CF surface liquid transport increased after carbachol stimulation. The stagnant CF mucus bundles were trapped on the tracheal surface attached to the surface goblet cells. Pseudomonas aeruginosa bacteria were moved by the mucus bundles in wild-type but not CF pigs. Acetylcholine thus uncouples airway surface liquid transport from transport of the surface mucus bundles as the bundles are dynamically inhibited by acetylcholine and the CFTR channel, explaining initiation of CF and COPD, and opening novel therapeutic windows.

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