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变应性鼻炎小鼠模型中的位点特异性致敏:上呼吸道在气道疾病中的作用

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

作者信息

McCusker Christine, Chicoine Martin, Hamid Qutayba, Mazer Bruce

机构信息

Division of Allergy and Immunology, Montreal Children's Hospital Research Institute and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

出版信息

J Allergy Clin Immunol. 2002 Dec;110(6):891-8. doi: 10.1067/mai.2002.130048.

DOI:10.1067/mai.2002.130048
PMID:12464956
Abstract

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.

摘要

背景

变应性鼻炎(AR)是最常见的特应性疾病,与哮喘密切相关。我们建立了一种AR小鼠模型,以研究鼻腔、支气管和全身对局部变应原刺激的免疫反应。

目的

本研究的目的是建立并表征一种AR小鼠模型。

方法

6至8周龄的BALB/c小鼠通过鼻内(局部)给予卵清蛋白(OVA)或全身腹腔注射进行致敏。然后用鼻内OVA对其进行激发,并评估过敏反应。

结果

发现鼻内颗粒沉积仅位于鼻孔。所有致敏动物在激发后OVA特异性血清IgE和IgG水平均升高,尽管达到最大反应的时间因所用变应原的途径和剂量而异。上、下呼吸道的组织学检查显示明显的嗜酸性粒细胞浸润,支气管肺泡灌洗液分析显示激发后IL-5和PMN浸润增加。

结论

通过对小鼠鼻孔进行单纯局部致敏和激发,我们能够证明上、下呼吸道均有炎症变化,尽管变应原颗粒似乎仅分布于这些动物的鼻孔。这为上呼吸道在气道疾病中的重要性提供了进一步证据。我们已经表明给药途径极大地影响后续免疫反应的特征。

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