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Published ahead of print on May 6, 2004, doi:10.1164/rccm.200301-030OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 306-312, (2004)
© 2004 American Thoracic Society


Original Article

Respiratory Syncytial Virus in Allergic Lung Inflammation Increases Muc5ac and Gob-5

Koichi Hashimoto, Barney S. Graham, Samuel B. Ho, Kenneth B. Adler, Robert D. Collins, Sandra J. Olson, Weisong Zhou, Tatsuo Suzutani, Phillip W. Jones, Kasia Goleniewska, Jamye F. O'Neal and R. Stokes Peebles, Jr.

Vanderbilt University, School of Medicine, Nashville, Tennessee; Viral Pathogenesis Laboratory and Clinical Trial Core, National Institutes of Health, Bethesda, Maryland; University of Minnesota, Veterans Affairs Medical Center, Minneapolis, Minnesota; North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina; and Fukushima Medical University, Fukushima, Japan

Correspondence and requests for reprints should be addressed to R. Stokes Peebles, Jr., M.D., Center for Lung Research, T-1217 MCN, Vanderbilt University Medical Center, Nashville, TN 37232-2650. E-mail: stokes.peebles{at}vanderbilt.edu

Respiratory syncytial virus (RSV) is associated with wheezing and childhood asthma. We previously reported that RSV infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin (OVA)-sensitized mice. In addition, allergically sensitized RSV-infected (OVA/RSV) mice had more abundant airway epithelial mucus production compared with OVA mice 14 days after infection, whereas there was almost no mucus in mice that were only RSV infected. We hypothesized that this increased mucus was associated with mucosal expression of Muc5ac, a mucus gene expression in airways, and gob-5, a member of the Ca2+-activated chloride channel family. By histochemical analysis, we found that there was significantly increased staining for gob-5 and Muc5ac in the airways of OVA/RSV mice compared with either OVA mice or allergically sensitized mice that were challenged with inactivated RSV, and virtually no detectable staining in the RSV group. These findings were confirmed by Western blot analysis. The increased mucus expression in the OVA/RSV group was associated with increased lung levels of interleukin-17, a factor known to stimulate airway mucin gene expression. The impact of virus infection combined with allergic inflammation on mucus production may partially explain the more severe disease and airway hyperresponsiveness associated with RSV in the setting of atopy.

Key Words: mucin • MUC5ac • gob-5 • respiratory syncytial virus




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