Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness.
A murine model for antigen-induced bronchial hyperreactivity (BHR) and airway eosinophilia, two hallmarks of asthma, was developed using ovalbumin-immunized mice, which produce large amounts of IgE (named BP2, "Bons Producteurs 2," for High Line of Selection 2). A single intranasal ovalbumin challenge failed to modify the bronchial responses, despite the intense eosinophil recruitment into the bronchoalveolar lavage fluid and airways. When mice were challenged twice a day for 2 days or once a day for 10 days, BHR in response to i.v. 5-hydroxytryptamine or to inhaled methacholine was induced in BP2 mice but not in BALB/c mice. Histological examination showed that eosinophils reached the respiratory epithelium after multiple ovalbumin challenges in BP2 mice but remained in the bronchial submucosa in BALB/c mice. Total IgE titers in serum were augmented significantly with immunization in both strains, but much more so in BP2 mice. Interleukin 5 (IL-5) titers in serum and bronchoalveolar lavage fluid of BP2 mice were augmented by the antigenic provocation, and a specific anti-IL5 neutralizing antibody suppressed altogether airway eosinophilia and BHR, indicating a participation of IL-5 in its development. Our results indicate that the recruitment of eosinophils to the airways alone does not induce BHR in mice and that the selective effect on BP2 mice is related to their increased IgE titers associated with antigen-driven eosinophil migration to the epithelium, following formation and secretion of IL-5.
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Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-Institut National de la Santé et de la Recherche Médicale 285, Paris, France.
Hailé
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Lefort
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Huerre
M
M
Vargaftig
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BB
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D004342:Drug Hypersensitivity / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D004848:Epithelium / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D015848:Interleukin-5 / Q000276:immunology / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D012701:Serotonin / Q000276:immunology*
D000941:Antigens; D015848:Interleukin-5; D016210:Methacholine Chloride; D012701:Serotonin; D007073:Immunoglobulin E; D010047:Ovalbumin