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

Abstract

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.Keywords. 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.

Pulmonary Endotoxin Tolerance Protects against Cockroach Allergen-Induced Asthma-Like Inflammation in a Mouse Model

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Rodent models of allergic rhinitis: Relevance to human pathophysiology

“…Strategies for histopathologic analyses should begin by consulting nasal diagrams generated by Mery et al [47], or using the approach proposed by Young [48]. We have also identified sensitive sites to evaluate respiratory epithelial populations in nasal septum, lateral wall, turbinates, and nasopharynx, where we have detected consistent epithelial responses in both allergic rats and mice [34,49]. Analysis of the nasolacrimal duct as a sensitive site for allergic rhinoconjunctivitis is almost completely ignored in rodent AR models.…”

Review of Mouse Models Applied to the Study of Asthma

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