Date of Award
Master of Science (MSc)
Medical Sciences (Division of Physiology/Pharmacology)
Mark D Inman
The airway epithelium, which acts as a protective barrier, is impaired in asthmatic patients and may contribute to abnormal airway function. Chronic inflammation, a feature of asthma, is associated with structural changes in the airway epithelium including the transformation of columnar epithelial cells into mucin secreting goblet cells. Human epithelial cells exposed to Interleukin-13 (IL-13) in vitro resulted in goblet cell metaplasia and a significant drop in transepithelial resistance, indicating that barrier function is impaired.
We sought to determine whether goblet cell metaplasia alone is sufficient to impair airway epithelial barrier function in vivo.
Female BALB/c mice were infected with an adenovirus to overexpress IL-13, a control adenovirus, or no virus. Barrier integrity was assessed via single-photon emission computed tomography (SPECT) imaging by measuring the dispersion of technetium-labeled diethylene triamine pentaacetic acid (99mTc-DTPA) out of the lungs over time. Lung sections were stained by Periodic acid-Schiff to detect the presence of mucin-containing goblet cells.
IL-13 exposure resulted in goblet cell metaplasia and associated airway hyperresponsiveness to methacholine. However, there was no significant increase in dispersion of 99mTc-DTPA over time from the airways in IL-13 overexpressed mice compared to control mice.
IL-13 induced goblet cell metaplasia did not impair the airway epithelial barrier to 99mTc-DTPA in our in vivo mouse model. Therefore, we conclude that epithelial dysfunction to DTPA observed in human asthmatics and in animal models of asthma are not due to IL-13 induced goblet cell metaplasia.
Dalle Ave, Christopher J., "The Effect of Goblet Cell Metaplasia On Airway Barrier Integrity" (2012). Open Access Dissertations and Theses. Paper 6554.
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