Impaired Mucus Detachment Disrupts Mucociliary Transport in a Piglet Model of Cystic Fibrosis

Mark Hoegger, Anthony Fischer, James McMenimen, Lynda Ostedgaard, Alexander Tucker, Maged Awadalla, Thomas Moninger, Andrew Michalski, Eric Hoffman, Joseph Zabner, David Stoltz, Michael Welsh

Research output: Contribution to journalArticlepeer-review

205 Citations (Scopus)

Abstract

Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment.

Original languageEnglish
Pages (from-to)818-822
Number of pages5
JournalScience
Volume345
Issue number6198
DOIs
Publication statusPublished - 15 Aug 2014

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