title: Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hoegger
authors.affiliation: Department of Pediatrics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Fischer
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: McMenimen
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Lynda S
authors.initials: LS
authors.lastname: Ostedgaard
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Tucker
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Maged A
authors.initials: MA
authors.lastname: Awadalla
authors.affiliation: Central Microscopy Research Facility, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Moninger
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Michalski
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Radiology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA. david-stoltz@uiowa.edu michael-welsh@uiowa.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Howard Hughes Medical Institute (HHMI), University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. david-stoltz@uiowa.edu michael-welsh@uiowa.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000838:Anions / Q000378:metabolism; D002923:Cilia / Q000502:physiology; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004195:Disease Models, Animal; D005088:Exocrine Glands / Q000378:metabolism*; D008168:Lung / Q000503:physiopathology; D016210:Methacholine Chloride / Q000494:pharmacology; D009079:Mucociliary Clearance; D009093:Mucus / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000503:physiopathology*; D012137:Respiratory System / Q000503:physiopathology*; D013552:Swine; D014132:Trachea / Q000503:physiopathology
chemical_list: D000838:Anions; D016210:Methacholine Chloride; D019005:Cystic Fibrosis Transmembrane Conductance Regulator