Sequential development of airway hyperresponsiveness and acute airway obstruction in a mouse model of allergic inflammation
Sequential development of airway hyperresponsiveness and acute airway obstruction in a mouse model of allergic inflammation
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DOI：
10.1159/000024298
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发表时间：
2000-01-01
影响因子：
2.8
通讯作者：
Renz, H
中科院分区：
文献类型：
--
作者：
Neuhaus-Steinmetz, U;Glaab, T;Renz, H
背景：已经建立了反映人类支气管哮喘关键特征的小鼠模型，包括气道高反应性（AHR）。然而，应对过敏原挑战的急性气道阻塞仍有待在这些模型中得到证实。目的：采用小鼠过敏性肺部炎症模型来分析特异性（过敏原诱导的）和非特异性（乙酰甲胆碱诱导的）气道阻塞的发展。方法：使小鼠对卵清蛋白 (OVA) 敏感，并在四个星期内每周两次用 OVA 气雾剂进行攻击。通过无创头出身体体积描记法测定肺功能的变化。通过呼气中期流速 (EF50) 的降低来评估 OVA 激发后急性气道阻塞的发展以及乙酰甲胆碱气雾剂应用后的 AHR 结果：两次气道激发足以诱导 AHR（5.7 与 15 mg/ml 乙酰甲胆碱）。进一步的 OVA 挑战将基线 EF50 从 1.85 降低至 1.20 ml/s（第 4 周）并诱发急性气道阻塞。 OVA 引起的阻塞在第 4 周达到最大（EF50 = 0.91 ml/s）。结论：通过头部体积描记法证实了过敏原致敏小鼠发生急性气道阻塞的情况。在我们的模型中，在气道阻塞发生之前观察到 AHR。版权所有 (C) 2000 S. Karger AG，巴塞尔。
Background: Mouse models have been established mirroring key features of human bronchial asthma including airway hyperresponsiveness (AHR). Acute airway obstruction in response to an allergen challenge, however, remains to be demonstrated in these models. Objective: A mouse model of allergic lung inflammation was employed to analyze the development of specific (allergen-induced) and nonspecific (methacholine-induced) airway obstruction. Methods: Mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol twice each week during four weeks. Changes in lung functions were determined by noninvasive head-out body plethysmography. The development of acute airway obstruction after OVA challenge and AHR after methacholine aerosol application were assessed by a decrease in the mid-expiratory flow rate (EF50) Results: Two airway challenges were sufficient to induce AHR (5.7 vs. 15 mg/ml methacholine). Further OVA challenges reduced the baseline EF50 from 1.85 to 1.20 ml/s (4th week) and induced acute airway obstruction. The OVA-induced obstruction was maximal in the 4th week (EF50 = 0.91 ml/s). Conclusion: The development of acute airway obstruction in allergen-sensitized mice was demonstrated by means of head-out body plethysmography. In our model, AHR was observed before the development of airway obstruction. Copyright (C) 2000 S. Karger AG, Basel.