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Immune Responses in the Lung and Local Lymph Node of A/J Mice to Intranasal Sensitization and Challenge with Adjuvant-Free Ovalbumin

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA 48824

Jack R. Harkema

Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA 48824

Tong-Rong Jan

Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan

Norbert E. Kaminski

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA 48824, kamins11{at}msu.edu

Pathologic features of IgE-mediated allergic airway diseases include airway infiltration of inflammatory cells (eg, lymphocytes, plasma cells, and eosinophils) and mucous cell metaplasia (MCM) in airway epithelium. CD4+ T lymphocytes, specifically those producing a type 2 (Th2) cytokine profile, are necessary for the induction of IgE-mediated allergic airway responses. Most experimental models of IgE-mediated allergic airway disease use systemic (eg, intraperitoneal) administration of an allergen coupled with an adjuvant to sensitize animals. Cytokine changes are measured in a number of ways including in bronchoalveolar lavage fluid (BALF) or lymph node cells stimulated ex vivo. The primary objective of this study was to test the hypothesis that intranasal sensitization and challenge of mice with ovalbumin in the absence of an adjuvant will induce the pathologic features that are characteristic of IgE-mediated allergic airway disease. Another objective was to determine if intranasal delivery of this allergen will result in the induction of a profile of cytokine gene expression in the lung and tracheobronchial (TB) lymph node, that is typical of immunologic changes associated with IgE-mediated allergic airway disease. Only mice that were intranasally sensitized and challenged with ovalbumin exhibited pulmonary lesions that included marked MCM in the respiratory epithelium lining the nasal and pulmonary airways, and an associated mixed inflammatory cell influx consisting of lymphocytes, plasma cells and eosinophils. Ovalbumin-treated mice also exhibited enhanced expression of the Th2 cytokine mRNAs IL-4, IL-5, IL-10, and IL-13 in the lung and IL-4 in the TB lymph node, and concurrent increases in ovalbumin-specific IgE in the serum. The results of this study indicate that A/J mice intranasally instilled with ovalbumin without adjuvant have the hallmark histopathologic and immunologic features of IgE-mediated allergic airway disease of humans.

Key Words: Intranasal sensitization and challenge • nasal and pulmonary airways • A/J mice • Th2 cytokines • ovalbumin • adjuvant-free • morphologic features of allergic airway disease • tracheobronchial lymph node.

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Toxicologic Pathology, Vol. 31, No. 4, 432-447 (2003)
DOI: 10.1080/01926230390213766


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Farraj, A. K. Articles by Kaminski, N. E. Search for Related Content PubMed PubMed Citation Articles by Farraj, A. K. Articles by Kaminski, N. E. Social Bookmarking                         What's this?