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Am J Physiol Gastrointest Liver Physiol 293: G383-G390, 2007. First published April 12, 2007; doi:10.1152/ajpgi.00341.2006
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INNOVATIVE METHODOLOGY

Eosinophilia is induced in the colon of Th2-sensitized mice upon exposure to locally expressed antigen

Qing Zhu,1,* Christopher W. Thomson,1,* Guofeng Zhang,3 Martin Stämpfli,1 Mark R. McDermott,1 Stephen M. Collins,2 and Jack Gauldie1

Departments of 1Pathology and Molecular Medicine, Center for Gene Therapeutics and 2Medicine, McMaster University, Hamilton, Ontario, Canada; and 3Laboratory of Bioengineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland

Submitted 26 July 2006 ; accepted in final form 23 March 2007

Eosinophilic inflammation is a feature of a variety of gastrointestinal (GI) disorders including eosinophil-associated GI disorder, allergy, inflammatory bowel disease, and parasite infection. Elucidating the mechanisms of eosinophil infiltration into the GI tract is important to the understanding of multiple disease processes. We hypothesize that eosinophilia in the large intestine (colon) can be induced by an antigen in a host that is associated with Th2-skewed antigen-specific immune responses. To investigate the importance of antigenic triggering, we established polarized antigen-specific Th2 type responses in BALB/c mice, using ovalbumin in conjunction with aluminum hydroxide. Upon challenge at the colonic mucosa through transient (3–4 days) expression of the antigen gene encoded in an adenovirus vector, sensitized animals developed significant subepithelial colonic inflammation, characterized by marked eosinophilic infiltration, and the presence of enlarged and increased numbers of lymphoid follicles. The alterations peaked around day 5 and resolved over the next 5–10 days, and no epithelial cell damage was detected through the entire course. Administration of a control (empty) adenovirus vector did not lead to any pathological changes. These data suggest that colonic eosinophilia can be induced by exposure to an antigen associated with preexisting Th2-skewed responses. Thus the model established here may provide a useful tool to study GI and, in particular, colonic inflammation with respect to underlying mechanisms involved in the recruitment and the immediate function of eosinophils.

mucosal; eosinophil; adenovirus; intrarectal



Address for reprint requests and other correspondence: Q. Zhu, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (e-mail: zhuq{at}mail.nih.gov)







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