Publication Date:
2014-08-16
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346163/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346163/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- DK054759/DK/NIDDK NIH HHS/ -- DP2 HL117744/DP/NCCDPHP CDC HHS/ -- DP2 HL117744/HL/NHLBI NIH HHS/ -- HL051670/HL/NHLBI NIH HHS/ -- HL091842/HL/NHLBI NIH HHS/ -- P01 HL051670/HL/NHLBI NIH HHS/ -- P01 HL091842/HL/NHLBI NIH HHS/ -- P30 DK054759/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):818-22. doi: 10.1126/science.1255825.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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 Pediatrics, 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. ; Central Microscopy Research Facility, 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 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. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124441" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Animals, Newborn
;
Anions/metabolism
;
Cilia/physiology
;
Cystic Fibrosis/*physiopathology
;
Cystic Fibrosis Transmembrane Conductance Regulator/physiology
;
Disease Models, Animal
;
Exocrine Glands/*secretion
;
Lung/physiopathology
;
Methacholine Chloride/pharmacology
;
*Mucociliary Clearance
;
Mucus/*secretion
;
Respiratory Mucosa/*physiopathology
;
Respiratory System/*physiopathology
;
Swine
;
Trachea/physiopathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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