eLife (Oct 2020)
Lack of airway submucosal glands impairs respiratory host defenses
- Lynda S Ostedgaard,
- Margaret P Price,
- Kristin M Whitworth,
- Mahmoud H Abou Alaiwa,
- Anthony J Fischer,
- Akshaya Warrier,
- Melissa Samuel,
- Lee D Spate,
- Patrick D Allen,
- Brieanna M Hilkin,
- Guillermo S Romano Ibarra,
- Miguel E Ortiz Bezara,
- Brian J Goodell,
- Steven E Mather,
- Linda S Powers,
- Mallory R Stroik,
- Nicholas D Gansemer,
- Camilla E Hippee,
- Keyan Zarei,
- J Adam Goeken,
- Thomas R Businga,
- Eric A Hoffman,
- David K Meyerholz,
- Randall S Prather,
- David A Stoltz,
- Michael J Welsh
Affiliations
- Lynda S Ostedgaard
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Margaret P Price
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Kristin M Whitworth
- Division of Animal Science, University of Missouri, Columbia, United States
- Mahmoud H Abou Alaiwa
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Anthony J Fischer
- Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Akshaya Warrier
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Melissa Samuel
- Division of Animal Science, University of Missouri, Columbia, United States
- Lee D Spate
- Division of Animal Science, University of Missouri, Columbia, United States
- Patrick D Allen
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Brieanna M Hilkin
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Guillermo S Romano Ibarra
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Miguel E Ortiz Bezara
- ORCiD
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Brian J Goodell
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Steven E Mather
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Linda S Powers
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Mallory R Stroik
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Nicholas D Gansemer
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Camilla E Hippee
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Keyan Zarei
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States; Department of Biomedical Engineering, University of Iowa, Iowa City, United States
- J Adam Goeken
- Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Thomas R Businga
- Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Eric A Hoffman
- ORCiD
- Department of Biomedical Engineering, University of Iowa, Iowa City, United States; Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- David K Meyerholz
- ORCiD
- Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Randall S Prather
- Division of Animal Science, University of Missouri, Columbia, United States
- David A Stoltz
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States; Department of Biomedical Engineering, University of Iowa, Iowa City, United States; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Michael J Welsh
- ORCiD
- Department of Internal Medicine and Pappajohn Biomedical Institute Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States; Howard Hughes Medical Institute, University of Iowa, Iowa City, United States
- DOI
- https://doi.org/10.7554/eLife.59653
- Journal volume & issue
-
Vol. 9
Abstract
Submucosal glands (SMGs) are a prominent structure that lines human cartilaginous airways. Although it has been assumed that SMGs contribute to respiratory defense, that hypothesis has gone without a direct test. Therefore, we studied pigs, which have lungs like humans, and disrupted the gene for ectodysplasin (EDA-KO), which initiates SMG development. EDA-KO pigs lacked SMGs throughout the airways. Their airway surface liquid had a reduced ability to kill bacteria, consistent with SMG production of antimicrobials. In wild-type pigs, SMGs secrete mucus that emerges onto the airway surface as strands. Lack of SMGs and mucus strands disrupted mucociliary transport in EDA-KO pigs. Consequently, EDA-KO pigs failed to eradicate a bacterial challenge in lung regions normally populated by SMGs. These in vivo and ex vivo results indicate that SMGs are required for normal antimicrobial activity and mucociliary transport, two key host defenses that protect the lung.
Keywords