A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model
A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model
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DOI：
10.1164/ajrccm.165.1.2105051
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发表时间：
2002-01-01
影响因子：
24.7
通讯作者：
Chi, EY
中科院分区：
文献类型：
--
作者：
Henderson, WR;Tang, LO;Chi, EY
慢性哮喘的气道炎症和重塑的特点是气道嗜酸性粒细胞增多、杯状细胞和平滑肌增生以及上皮下纤维化。我们研究了白三烯在过敏原诱导的慢性肺部炎症和纤维化小鼠模型中的作用。BALB/c小鼠在第0天和第14天经腹腔注射卵清蛋白(OVA)致敏后，在第14-75天定期鼻腔注射OVA。OVA处理的小鼠出现广泛的嗜酸性粒细胞和单核细胞炎症反应，杯状细胞增生，呼吸道粘液阻塞。这种炎症反应的一个显着特征是广泛的胶原沉积在呼吸道上皮细胞层下，也在肺间质中白细胞浸润的部位，这在生理盐水对照组中没有观察到。半胱氨酰白三烯(1)(CysLT(1))受体拮抗剂孟鲁司特显著减轻OVA致敏/激发小鼠的气道嗜酸粒细胞浸润、粘液堵塞、平滑肌增生和上皮下纤维化。CysLT(1)受体拮抗剂还可抑制OVA组小鼠肺巨噬细胞中Charcot-Leyden样晶体的存在，以及肺组织中IL-4和IL-13mRNA表达的增加以及BAL液中蛋白质的增加。这些数据表明，半胱氨酰白三烯在慢性过敏性气道炎症伴纤维化的发病机制中起重要作用。
Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis.