Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models
Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models
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DOI：
10.1016/j.jaci.2003.07.005
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发表时间：
2003-11-01
影响因子：
14.2
通讯作者：
Nel, A
中科院分区：
文献类型：
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作者：
Hao, MQ;Comier, S;Nel, A
背景：流行病学研究表明，环境颗粒物(PM)水平的突然飙升可引发急性哮喘加重。虽然柴油机尾气微粒(DEPS)可作为过敏性致敏的佐剂，但这是一种延迟反应，不能解释急性PM对气道高反应性(AHR)的影响。目的：我们的目的是利用小鼠模型来确定DEPS对AHR的急性影响。方法：制定了三种方案，其中两种需要OVA增敏，第三种方案不依赖OVA。在温和致敏方案中，BALB/c小鼠接受不含明矾的OVA腹腔注射，然后用含或不含DEPS的雾化OVA激发。在激发后模型中，用卵清蛋白加明矾致敏的动物，在卵清蛋白激发后注射DEPS。在第三个方案中，雾化器DEPS也被输送到IL-5过度表达的小鼠身上，这些小鼠表现出结构性的呼吸道炎症。动物进行全身体积描记(WBP)，然后处死动物进行支气管肺泡灌洗、组织学和血清学检查。结果：在模型1和模型2中，DEP递送伴随着OVA攻击或在用该变应原诱导呼吸道炎症后分别导致AHR增加。虽然这些动物表现出DEP诱导的炎症和中间呼吸道粘液的产生，但对OVA特异性IgE或T(H)2细胞因子的产生没有影响。在IL-5转基因小鼠中，在没有过敏原的情况下，DEPS可以诱导类似的效应。结论：我们证明了DEPS诱导的AHR不依赖于它们的佐剂作用，提示我们可以利用这些模型来研究哮喘急性加重的机制。
Background: Epidemiologic studies show that sudden surges in ambient particulate matter (PM) levels can trigger acute asthma exacerbations. Although diesel exhaust particles (DEPs) act as an adjuvant for allergic sensitization, this is a delayed response and does not explain acute PM effects on airway hyperreactivity (AHR).Objective: Our aim was to determine the acute effects of DEPs on AHR using a mouse model.Methods: Three protocols were developed, 2 of which require OVA sensitization, whereas the third was OVA independent. In the mild sensitization protocol BALB/c mice receive intraperitoneal OVA without alum and are then challenged with aerosolized OVA with or without DEPs. In the postchallenge model DEPs are delivered after OVA challenge to animals sensitized by intraperitoneal OVA plus alum. In the third protocol nebulizer DEPs were also delivered to IL-5-overexpressing mice that exhibit constitutive airway inflammation. Animals were subjected to whole-body plethysmography (WBP) and then killed for performance of bronchoalveolar lavage, histology, and serology.Results: DEP delivery concomitant with OVA challenge or after the induction of airway inflammation with this allergen induced increased AHR in models 1 and 2, respectively. Although these animals showed DEP-induced inflammation and mucus production in the intermediary airways, there was no effect on OVA-specific IgE or T(H)2 cytokine production. In the IL-5 transgenic mice it was possible to induce similar effects with DEPs in the absence of an allergen.Conclusion: We demonstrate that DEPs induced AHR independent of their adjuvant effects, suggesting the use of these models to study the mechanism or mechanisms of acute asthma exacerbation by means of PM.