Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways

Sandra K. Gilley, Antine E. Stenbit, Raymond C. Pasek, Kelli M. Sas, Stacy L. Steele, May Amria, Marlene A. Bunni, Kimberly P. Estell, Lisa M. Schwiebert, Patrick Flume, Monika Gooz, Courtney J. Haycraft, Bradley K. Yoder, Caroline Miller, Jacqueline A. Pavlik, Grant A. Turner, Joseph Harold Sisson, P. Darwin Bell

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The mechanisms for the development of bronchiectasis and airway hyperreactivity have not been fully elucidated. Although genetic, acquired diseases and environmental influences may play a role, it is also possible that motile cilia can influence this disease process. We hypothesized that deletion of a key intraflagellar transport molecule, IFT88, in mature mice causes loss of cilia, resulting in airway remodeling. Airway cilia were deleted by knockout of IFT88, and airway remodeling and pulmonary function were evaluated. In IFT88~ mice there was a substantial loss of airway cilia on respiratory epithelium. Three months after the deletion of cilia, there was clear evidence for bronchial remodeling that was not associated with inflammation or apparent defects in mucus clearance. There was evidence for airway epithelial cell hypertrophy and hyperplasia. IFT88~ mice exhibited increased airway reactivity to a methacholine challenge and decreased ciliary beat frequency in the few remaining cells that possessed cilia. With deletion of respiratory cilia there was a marked increase in the number of club cells as seen by scanning electron microscopy. We suggest that airway remodeling may be exacerbated by the presence of club cells, since these cells are involved in airway repair. Club cells may be prevented from differentiating into respiratory epithelial cells because of a lack of IFT88 protein that is necessary to form a single nonmotile cilium. This monocilium is a prerequisite for these progenitor cells to transition into respiratory epithelial cells. In conclusion, motile cilia may play an important role in controlling airway structure and function.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume306
Issue number2
DOIs
StatePublished - Jan 15 2014

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Bronchiectasis
Cilia
Airway Remodeling
Epithelial Cells
Respiratory Mucosa
Inborn Genetic Diseases
Methacholine Chloride
Mucus
Electron Scanning Microscopy
Hypertrophy
Hyperplasia
Stem Cells
Cell Count
Inflammation
Lung

Keywords

  • Bronchiectasis
  • Hyperreactivity
  • Lung
  • Respiratory

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways. / Gilley, Sandra K.; Stenbit, Antine E.; Pasek, Raymond C.; Sas, Kelli M.; Steele, Stacy L.; Amria, May; Bunni, Marlene A.; Estell, Kimberly P.; Schwiebert, Lisa M.; Flume, Patrick; Gooz, Monika; Haycraft, Courtney J.; Yoder, Bradley K.; Miller, Caroline; Pavlik, Jacqueline A.; Turner, Grant A.; Sisson, Joseph Harold; Bell, P. Darwin.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 306, No. 2, 15.01.2014.

Research output: Contribution to journalArticle

Gilley, SK, Stenbit, AE, Pasek, RC, Sas, KM, Steele, SL, Amria, M, Bunni, MA, Estell, KP, Schwiebert, LM, Flume, P, Gooz, M, Haycraft, CJ, Yoder, BK, Miller, C, Pavlik, JA, Turner, GA, Sisson, JH & Bell, PD 2014, 'Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 306, no. 2. https://doi.org/10.1152/ajplung.00095.2013
Gilley, Sandra K. ; Stenbit, Antine E. ; Pasek, Raymond C. ; Sas, Kelli M. ; Steele, Stacy L. ; Amria, May ; Bunni, Marlene A. ; Estell, Kimberly P. ; Schwiebert, Lisa M. ; Flume, Patrick ; Gooz, Monika ; Haycraft, Courtney J. ; Yoder, Bradley K. ; Miller, Caroline ; Pavlik, Jacqueline A. ; Turner, Grant A. ; Sisson, Joseph Harold ; Bell, P. Darwin. / Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2014 ; Vol. 306, No. 2.
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AU - Estell, Kimberly P.

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AU - Haycraft, Courtney J.

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AU - Turner, Grant A.

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