The importance of leukotrienes in airway inflammation in a mouse model of asthma.
The importance of leukotrienes in airway inflammation in a mouse model of asthma.
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DOI：
10.1084/jem.184.4.1483
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发表时间：
1996-10-01
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中科院分区：
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免疫小鼠吸入抗原会导致嗜酸性粒细胞渗入呼吸道，并增加支气管的高反应性，就像在人类哮喘中观察到的那样。我们采用小鼠晚期变态反应性肺部炎症模型来研究白三烯(LT)在介导气道嗜酸性粒细胞增多和对乙酰甲胆碱的高反应性中的作用。OVA致敏小鼠的过敏原鼻腔攻击导致LTB4和LTC4释放到空气中，呼吸道广泛的粘液阻塞，呼吸道组织和以嗜酸性粒细胞为主的支气管肺泡灌洗液中的白细胞渗透，以及对乙酰胆碱的高反应性。5-脂氧合酶和5-脂氧合酶激活蛋白的特异性抑制剂阻断嗜酸性粒细胞的气道黏液释放和渗透，表明白三烯在过敏性肺部炎症的这些特征中起关键作用。然而，在这个小鼠模型中，白三烯或嗜酸性粒细胞在介导呼吸道对空气变应原的高反应性中的作用尚不能确定。
Inhalation of antigen in immunized mice induces an infiltration of eosinophils into the airways and increased bronchial hyperreactivity as are observed in human asthma. We employed a model of late-phase allergic pulmonary inflammation in mice to address the role of leukotrienes (LT) in mediating airway eosinophilia and hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensitized mice induced LTB4 and LTC4 release into the airspace, widespread mucus occlusion of the airways, leukocytic infiltration of the airway tissue and broncho-alveolar lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to methacholine. Specific inhibitors of 5- lipoxygenase and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these features of allergic pulmonary inflammation. The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine model.