Site-specific sensitization in a murine model of allergic rhinitis: Role of the upper airway in lower airways disease

Site-specific sensitization in a murine model of allergic rhinitis: Role of the upper airway in lower airways disease
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DOI:
10.1067/mai.2002.130048
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发表时间:
2002-12-01
影响因子:
14.2
通讯作者:
Mazer, B
Mazer, B
中科院分区:
医学1区
文献类型:
--
作者:
McCusker, C;Chicoine, M;Mazer, B

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背景:过敏性鼻炎(AR)是最常见的特应性疾病,与哮喘有密切联系。我们已经开发了一种小鼠模型AR研究鼻,支气管和全身免疫反应局部过敏原stimulation.Objectives:本研究的目的是开发和表征小鼠模型AR。方法:6 - 8周龄BALB/c小鼠致敏通过鼻内(局部)应用卵清蛋白(OVA)或全身腹腔注射。然后,他们与鼻内卵清蛋白的挑战,过敏反应assessed.Results:鼻内颗粒沉积被发现是专门在鼻孔。所有致敏动物在激发后显示出OVA特异性血清IgE和IgG水平升高,尽管最大反应的时间随所用变应原的途径和剂量而变化。组织学的上,下呼吸道表现出显着的嗜酸性粒细胞浸润,和支气管肺泡灌洗液的分析显示增加IL-5和PMN infiltration后challenge.Conclusion:使用独家局部致敏和小鼠鼻孔的挑战,我们能够证明炎症的变化,在上,下呼吸道,即使,过敏原颗粒的分布似乎只在这些动物的鼻孔。这进一步证明了上呼吸道在下呼吸道疾病中的重要性。我们已经表明,给药途径极大地影响了随后的免疫反应的特征。
Background: Allergic rhinitis (AR) is the most common atopic disease with strong links to asthma. We have developed a murine model of AR to study nasal, bronchial, and systemic immune response to local allergen stimulation.Objectives: The purpose of this study was to develop and characterize a murine model of AR.Methods: Six- to 8-week-old BALB/c mice were sensitized by means of intranasal (local) application of ovalbumin (OVA) or systemic intraperitoneal injection. They were then challenged with intranasal OVA, and allergic response was assessed.Results: Intranasal particle deposition was found to be exclusively in the nares. All sensitized animals showed increased levels of OVA-specific serum IgE and IgG after challenge, although the timing to maximal response varied with the route and dose of allergen used. Histology of the upper and lower airways showed marked eosinophilic infiltration, and analysis of bronchoalveolar lavage fluid showed increased IL-5 and PMN infiltrates after challenge.Conclusion: Using exclusive local sensitization and challenge of mouse nares, we were able to demonstrate inflammatory changes in both the upper and lower airways, even though, distribution of allergen particles appeared to be only in the nares of these animals. This provides further evidence for the importance of the upper airway in lower airways disease. We have shown that the route of administration greatly affects the characteristics of the subsequent immune responses.