Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis

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 occu...

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Published inScience (American Association for the Advancement of Science) Vol. 345; no. 6198; pp. 818 - 822
Main Authors Hoegger, Mark J., Fischer, Anthony J., McMenimen, James D., Ostedgaard, Lynda S., Tucker, Alex J., Awadalla, Maged A., Moninger, Thomas O., Michalski, Andrew S., Hoffman, Eric A., Zabner, Joseph, Stoltz, David A., Welsh, Michael J.
Format Journal Article
LanguageEnglish
Published United States American Association for the Advancement of Science 15.08.2014
The American Association for the Advancement of Science
Subjects
A defects
Airways
Animals
Animals, Newborn
Anions - metabolism
Body fluids
Cilia - physiology
Cystic fibrosis
Cystic Fibrosis - physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator - physiology
Disease Models, Animal
Exocrine Glands - metabolism
Hogs
Lung - physiopathology
Lungs
Methacholine Chloride - pharmacology
Mucociliary Clearance
Mucus
Mucus - metabolism
Plugging
Respiratory Mucosa - physiopathology
Respiratory System - physiopathology
Strands
Swine
Trachea - physiopathology
Transport
Walls
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Summary: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.
Bibliography:ObjectType-Article-1
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ISSN:0036-8075
1095-9203
DOI:10.1126/science.1255825