title: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Jan
authors.forename: Norbert E
authors.initials: NE
authors.lastname: Kaminski
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D001985:Bronchial Provocation Tests / Q000379:methods; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin