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

Details

• Alternative Title:
  Science
• Personal Author:
  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.
• Description:
  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.
• Subjects:
  Animals Animals, Newborn Anions Article Cilia Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Disease Models, Animal Exocrine Glands Lung Methacholine Chloride Mucociliary Clearance Mucus Respiratory Mucosa Respiratory System Swine Trachea

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• Source:
  Science. 345(6198):818-822.
• Pubmed ID:
  25124441
• Pubmed Central ID:
  PMC4346163
• Document Type:
  Journal Article
• Funding:
  DK054759/DK/NIDDK NIH HHS/United States ; DP2 HL117744/DP/NCCDPHP CDC HHS/United States ; DP2 HL117744/HL/NHLBI NIH HHS/United States ; HL051670/HL/NHLBI NIH HHS/United States ; HL091842/HL/NHLBI NIH HHS/United States ; P01 HL051670/HL/NHLBI NIH HHS/United States ; P01 HL091842/HL/NHLBI NIH HHS/United States ; Howard Hughes Medical Institute/United States ; Howard Hughes Medical Institute/United States
• Volume:
  345
• Issue:
  6198
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:50981ab67c458d756483200ac9a46f7379f27bcc8df034242b963a8bd02a0e04
• Download URL:
  https://stacks.cdc.gov/view/cdc/30313/cdc_30313_DS1.pdf
• File Type:
  [PDF - 654.83 KB ]