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Published ahead of print on May 6, 2004, doi:10.1164/rccm.200301-030OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 3, August 2004, 306-312

A more recent version of this article appeared on August 1, 2004
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Submitted on January 9, 2003
Accepted on April 30, 2004

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

Koichi Hashimoto1, Barney S Graham2, Samuel B Ho3, Kenneth B Adler4, Robert D Collins1, Sandra J Olson1, Weisong Zhou1, Tatsuo Suzutani5, Phillip W Jones1, Kasia Goleniewska1, Jamye F O'Neal1, and R. Stokes Peebles Jr.1*

1 School of Medicine, Vanderbilt University, Nashville, TN, USA, 2 Viral Pathogenesis Laboratory and Clinical Trial Core, VRC/NIAID/NIH, Bethesda, MD, USA, 3 Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN, USA, 4 College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA, 5 Microbiology, Fukushima Medical University, Fukushima, Japan

* To whom correspondence should be addressed. 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 (AHR) in ovalbumin-sensitized (OVA) mice. In addition, allergically-sensitized RSV-infected (OVA/RSV) mice had more abundant airway epithelial mucus production compared to OVA mice 14 days after infection, while there was almost no mucus in mice that were only RSV infected (RSV). 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 to either OVA mice or allergically sensitized mice that were challenged with inactivated RSV (OVA/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 IL-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 AHR associated with RSV in the setting of atopy.
Key words: RSV, mucin, Muc5ac, gob-5




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