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http://hdl.handle.net/11375/11597
Title: | The Effect of Goblet Cell Metaplasia On Airway Barrier Integrity |
Authors: | Dalle, Ave J Christopher |
Advisor: | Inman, Mark D Janssen, Luke Jordana, Manel |
Department: | Medical Sciences (Division of Physiology/Pharmacology) |
Keywords: | epithelial barrier;IL-13;asthma;Biological Phenomena, Cell Phenomena, and Immunity;Circulatory and Respiratory Physiology;Biological Phenomena, Cell Phenomena, and Immunity |
Publication Date: | Apr-2012 |
Abstract: | <p><strong>Introduction</strong></p> <p>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) <em>in vitro</em> resulted in goblet cell metaplasia and a significant drop in transepithelial resistance, indicating that barrier function is impaired.</p> <p><strong>Aim</strong></p> <p>We sought to determine whether goblet cell metaplasia alone is sufficient to impair airway epithelial barrier function <em>in vivo</em>.</p> <p><strong>Methods</strong></p> <p>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 (<sup>99m</sup>Tc-DTPA) out of the lungs over time. Lung sections were stained by Periodic acid-Schiff to detect the presence of mucin-containing goblet cells.</p> <p><strong>Results</strong></p> <p>IL-13 exposure resulted in goblet cell metaplasia and associated airway hyperresponsiveness to methacholine. However, there was no significant increase in dispersion of <sup>99m</sup>Tc-DTPA over time from the airways in IL-13 overexpressed mice compared to control mice.</p> <p><strong>Conclusion</strong></p> <p>IL-13 induced goblet cell metaplasia did not impair the airway epithelial barrier to <sup>99m</sup>Tc-DTPA in our <em>in vivo</em> 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.</p> |
URI: | http://hdl.handle.net/11375/11597 |
Identifier: | opendissertations/6554 7523 2345943 |
Appears in Collections: | Open Access Dissertations and Theses |
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