Takano H, Ichinose T, Miyabara Y, Shibuya T, Lim H B, Yoshikawa T, Sagai M
Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, Ibaraki, Japan.
Toxicol Appl Pharmacol. 1998 Jun;150(2):328-37. doi: 10.1006/taap.1998.8437.
We have previously shown that intratracheal instillation of suspension of diesel exhaust particles enhances allergen-related eosinophilic airway inflammation, airway hyperresponsiveness, and local expression of interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present study was designed to elucidate the effects of daily inhalation of diesel exhaust (DE) on the allergen-related respiratory disease. ICR mice were exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen-related eosinophil recruitment to the submucosal layers of the airways and to the bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the lung in a dose-dependent manner compared to exposure to clean air. There were strong correlations between the number of eosinophils in bronchoalveolar lavage (BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue supernatants. In addition, the increases in eosinophil recruitment and local cytokine expression were accompanied by goblet cell proliferation in the bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In contrast, the control mice exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no eosinophil recruitment to the submucosal layers of the airways nor to the bronchoalveolar space and few goblet cells in the bronchial epithelium. The present study provides experimental evidence that daily inhalation of DE can enhance allergen-related respiratory diseases such as allergic asthma. This effect may be mediated by the enhanced local expression of IL-5 and GM-CSF. Increased ambient levels of DE may be implicated in the increasing prevalence of bronchial asthma in recent years.
我们之前已经表明，气管内滴注柴油废气颗粒悬浮液可增强小鼠体内与过敏原相关的嗜酸性气道炎症、气道高反应性以及白细胞介素（IL）-5和粒细胞巨噬细胞集落刺激因子（GM-CSF）的局部表达。本研究旨在阐明每日吸入柴油废气（DE）对与过敏原相关的呼吸系统疾病的影响。在暴露的最后24周期间，将ICR小鼠每隔3周暴露于清洁空气或浓度为0.3、1.0或3.0 mg/m³的柴油废气中，并进行气溶胶过敏原激发（在等渗盐水中含1%卵清蛋白，持续6分钟），共暴露40周。与暴露于清洁空气相比，暴露于柴油废气以剂量依赖的方式增强了与过敏原相关的嗜酸性粒细胞向气道黏膜下层和支气管肺泡腔的募集，并增加了肺中GM-CSF和IL-5的蛋白质水平。支气管肺泡灌洗（BAL）液中的嗜酸性粒细胞数量与BAL上清液和肺组织上清液中的IL-5浓度之间存在强相关性。此外，嗜酸性粒细胞募集和局部细胞因子表达的增加伴随着支气管上皮杯状细胞增殖以及对吸入乙酰胆碱的气道高反应性。相比之下，在无过敏原激发的情况下，暴露于清洁空气或浓度为0.3、1.0或3.0 mg/m³的柴油废气40周的对照小鼠未出现嗜酸性粒细胞向气道黏膜下层或支气管肺泡腔的募集，且支气管上皮中的杯状细胞很少。本研究提供了实验证据，表明每日吸入柴油废气可增强与过敏原相关的呼吸系统疾病，如过敏性哮喘。这种效应可能是由IL-5和GM-CSF局部表达增强介导的。近年来环境中柴油废气水平的增加可能与支气管哮喘患病率的上升有关。
