The role of toll-like receptor 4 in environmental airway injury in mice
The role of toll-like receptor 4 in environmental airway injury in mice
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DOI：
10.1164/rccm.200311-1499oc
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发表时间：
2004-07-15
影响因子：
24.7
通讯作者：
Schwartz, DA
中科院分区：
文献类型：
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作者：
Hollingsworth, JW;Cook, DN;Schwartz, DA
吸入空气污染中常见的毒素有助于哮喘和环境气道损伤的发生和发展。在这项研究中，我们研究了toll样受体4 （TLR4）在小鼠肺部对三种环境毒素的反应中的需求：雾化脂多糖，颗粒物（残油粉煤灰）和臭氧。对这些毒素的生理和生物反应通过气道反应程度、中性粒细胞向下呼吸道募集、炎症细胞因子的变化和灌洗液中蛋白质的浓度来评估。经过基因工程处理的TLR4缺陷小鼠（C57BL/6(TLR4-/-)）对吸入的脂多糖没有反应，除了一些炎症细胞因子的轻微增加。相比之下，C57BL/6（TLR4-/-）小鼠对注入残油、粉煤灰或急性臭氧暴露的气道反应与野生型小鼠没有差异；然而，我们发现，尽管有强烈的炎症反应，C57BL/6（TLR4-/-）小鼠在亚慢性臭氧暴露后可防止气道高反应性的发展。这些数据表明，在小鼠中，TLR4对肺部炎症的需求取决于毒素的性质，并且似乎对毒素和暴露条件具有特异性。
Inhalation of toxins commonly found in air pollution contributes to the development and progression of asthma and environmental airway injury. In this study, we investigated the requirement of toll-like receptor 4 (TLR4) in mice for pulmonary responses to three environmental toxins: aerosolized lipopolysaccharide, particulate matter (residual oil fly ash), and ozone. The physiologic and biologic responses to these toxins were evaluated by the extent of airway responsiveness, neutrophil recruitment to the lower respiratory tract, changes in inflammatory cytokines, and the concentration of protein in the lavage fluid. Genetically engineered, TLR4-deficient mice (C57BL/6(TLR4-/-)) were unresponsive to inhaled lipopolysaccharide, except for minimal increases in some inflammatory cytokines. In contrast, C57BL/6(TLR4-/-) mice did not differ from wild-type mice in their airway response to instilled residual oil fly ash or acute ozone exposure; however, we found that, despite a robust inflammatory response, C57BL/6(TLR4-/-) mice are protected against the development of airway hyperresponsiveness after subchronic ozone exposure. These data demonstrate in the mouse that the requirement of TLR4 for pulmonary inflammation depends on the nature of the toxin and appears specific to toxin and exposure conditions.