A novel mouse model of experimental asthma
A novel mouse model of experimental asthma
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DOI：
10.1159/000074902
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Kleeberger, SR
中科院分区：
文献类型：
--
作者：
Sarpong, SB;Zhang, LY;Kleeberger, SR
背景资料：模拟人类哮喘中观察到的肺特征的动物模型是研究过敏原诱导的哮喘机制的重要工具。蟑螂和尘螨过敏原是两种常见的过敏原发现在'内城'的环境。本文研究了重组蟑螂（rBla g 2）和尘螨（rDer f 1）变应原在近交系小鼠（A/J）中的相互作用。所检验的假设是，在A/J小鼠中，暴露于r Bla g 2和r Der f 1变应原在气道炎症反应中有增强效应。研究方法：检查了五组小鼠（雄性，6-8周）：载体（盐水）对照;佐剂（明矾）对照; rBla g 2免疫（0.01-10 μ g/小鼠）、rDer f 1免疫（0.01 -10 μ g/小鼠）和rDer f 1（0.05 μ g/小鼠）和rBla g 2（0.05 μ g/小鼠）的联合免疫.在第0天和第7天免疫小鼠，在第14天通过经口气管吸入r Der f 1和/或r Bla g 2变应原进行攻击，并在第17天进行研究和处死。采用气道峰压和气道压力时间指数（APTI）测定气道高反应性。采用细胞差异分析和支气管肺泡灌洗液中的总蛋白来评估气道炎症和上皮损伤。结果如下：在r Bla g 2免疫小鼠中，r Bla g 2激发诱导了峰值压力、APTI、总细胞、嗜酸性粒细胞、上皮细胞（但不包括总蛋白）的剂量相关统计学显著性增加。在r Der f 1免疫小鼠中观察到气道总细胞、嗜酸性粒细胞、上皮细胞和总蛋白的相似变应原诱导的剂量相关性增加。与单独的过敏原相比，联合组中检测到气道炎症和上皮损伤增强，但未检测到气道反应性。结论：这种新的小鼠模型将允许人类哮喘的免疫发病机制的调查，并应提供洞察常见形式的“内城哮喘”。版权所有（C）2003 S. Karger AG，巴塞尔。
Background: Animal models that mimic the pulmonary features observed in human asthma are important tools to study the mechanism(s) of allergen-induced asthma. Cockroach and dust mite allergens are two common allergens found in the 'inner city' environment. In this study, we examined the interaction between recombinant cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain (A/J). The tested hypothesis was that there are enhanced effects of exposure to r Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice. Methods: Five groups of mice (male, 6-8 weeks) were examined: vehicle (saline) controls; adjuvant ( alum) controls; r Bla g 2 immunized (0.01-10 mug/mouse), r Der f 1 immunized (0.01-10 mug/mouse), and combined immunization with r Der f 1 (0.05 mug/mouse) and r Bla g 2 (0.0 5 mug/mouse). Mice were immunized at days 0 and 7, challenged by orotracheal inhalation with r Der f 1 and/or r Bla g 2 allergen at day 14, and were studied and sacrificed on day 17. Airway hyperreactivity was measured by peak airway pressure and airway pressure time index (APTI). Differential cell analysis and total proteins in bronchoalveolar lavage returns were used to assess airway inflammation and epithelial injury. Results: Dose-related statistically significant increases in peak pressure, APTI, total cells, eosinophils, epithelial cells, but not total proteins, were induced by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose-related increases in airway total cells, eosinophils, epithelial cells and total proteins were observed in r Der f 1 immunized mice. Compared to either allergen alone, enhanced airway inflammation and epithelial damage, but not airway reactivity, were detected in the combined group. Conclusion: This novel mouse model will allow investigation of the immunopathogenesis of human asthma and should provide insight into the common form of 'inner city asthma'. Copyright (C) 2003 S. Karger AG, Basel.