TY - JOUR T1 - The mucin bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00457-2018 SP - 1800457 AU - Anna Ermund AU - Lauren N. Meiss AU - Brendan Dolan AU - Andrea Bähr AU - Nikolai Klymiuk AU - Gunnar C. Hansson Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/05/17/13993003.00457-2018.abstract N2 - The beneficial effect of anti-cholinergic therapy for chronic obstructive pulmonary diseases like COPD is well-documented although cholinergic stimulation paradoxically inhibits liquid absorption, increases cilia beat frequency, and increases airway surface liquid transport.Using pig tracheobronchial explants, we quantified basal mucus transport as well as after incubation with by the clinically used anti-muscarinic compound ipratropium bromide (Atrovent) and stimulation with acetylcholine.As expected the 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 CFTR channel, the mucin bundles were almost immobile. As in wild-type pigs the cystic fibrosis (CF) surface liquid transport increased after carbachol stimulation. The stagnant CF mucin 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 mucin bundles as the bundles are dynamically inhibited by acetylcholine and the CFTR channel, explaining initiation of CF and COPD and opening novel therapeutic windows.Acetylcholine uncouples airway surface liquid transport from transport of the mucus bundles and lack of CFTR inhibits bundle movementFootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Ermund has nothing to disclose.Conflict of interest: Dr. Meiss has nothing to disclose.Conflict of interest: Dr. Dolan has nothing to disclose.Conflict of interest: Dr. Bähr has nothing to disclose.Conflict of interest: Dr. Klymiuk has nothing to disclose.Conflict of interest: Dr. Hansson reports grants from NIH, ERC, Wallenberg, Lederhausen, CFF, during the conduct of the study. ER -