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Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation

机译:卵清蛋白敏化小鼠是气道高反应性的良好模型,但对过敏原吸入不是急性生理反应

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Background: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. Objective: To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. Methods: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. Results: An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. Conclusions: The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.
机译:背景:哮喘是一种慢性炎症性疾病,临床上以对支气管收缩剂的气道高反应性(AHR)为特征。哮喘肺对吸入性变应原的生理反应通常以两个不同的阶段为特征:暴露后第一小时内的早期反应(EPR)消退,而长期反应(LPR)则更长时间并可能发生几个小时后。哮喘小鼠模型已经越来越流行,应该设计为具有EPR,LPR和AHR。目的:确定哮喘的常见模型是否能够证明EPR,LPR和AHR。方法:将BALB / c小鼠对卵清蛋白(OVA)致敏并用一种或三种OVA气雾剂攻击。使用低频强制振荡技术(LFOT)的改进评估了响应吸入过敏原的肺力学变化。为了评估AHR,使用LFOT评估了气雾化乙酰甲胆碱的肺力学变化。通过支气管肺泡灌洗(BAL)测量炎性细胞向肺的浸润。 ELISA用于测量BAL中的炎性细胞因子和血清中IgE的水平。结果:仅在大约一半的研究小鼠中,在接种了3种OVA气雾剂之后才检测到EPR。尽管在变应原刺激后6小时细胞浸润明显增加,但没有LPR的证据。 AHR出现在单个OVA气雾剂之后,但不出现在三个OVA气雾剂之后。结论:缺乏LPR,有限的EPR以及LPR和AHR之间没有联系,突显了该小鼠模型作为与哮喘相关的肺功能障碍的完整模型的局限性。

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