Experimental study on pathogenesis of asthma like symptom caused by combination of diesel exhaust and allergen.

柴油机尾气与过敏原联合引起哮喘样症状发病机制的实验研究

• 批准号: 10680528
• 负责人: ICHINOSE Takamichi
• 金额: $ 1.47万
• 依托单位: Oita University of Nursing and Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680528/
• 关键词: Diesel exhaust; Bronchial astma; Ovalbumin; Cytokine; Eosinophils; Goblet cells; IgE production; IgG1 produciton; 粘液細胞; IgG1抗体

We investigated the histopahologic changes in the airway by long term exposure to diesel exhaust (DE), ovalbumin (OA) treatment or the both combination. The relation between the histopahologic appearances in the airway and immunoglobulin production or levels of local cytokines in the lungs was also studies. ICR mice were exposed to clean air or DE at a soot concentrations of 0.3, 1.0 or 3.0 mg/mィイD13ィエD1 for 34 or 40 weeks. Fifteen weeks after exposures to DE, mice were sensitized intraperitonealy with 10 μg of OA, and challenged aerosol of 1% OA at 3-week intervals during the last 18 or 24 weeks of the exposures. Exposure to DE for 34 weeks caused dose-dependent increases of the typical changes such as non-ciliated cell proliferation and epithelial cell hypertrophy in the airway, but showed no effect on goblet cell proliferation in the bronchial epithelium and eosinophil recruitment in the airway. OA challenge induced very alight changes in goblet cell proliferation and eosinophil rec … More ruitment. The combination of OA and DE exposure at 3.0 mg/mィイD13ィエD1 produced increased changes of goblet cells and eosinophils, in addition to further increases of the typical changes induced by DE. "Exposure to DE at 3.0 mg/mィイD13ィエD1 for 40 weeks also enhanced allergen-induced eosinophil recruitment into the submucos in the airways, and increased protein levels of GM-CSF and IL-5 in the lungs. The increases in the eosinophil recruitment and the local cytokine expression were accompanied by those in goblet cell proliferation in the bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. OA treatment induced OA-specific IgG1 and IgE production in plasma, whereas the adjutant effects of DE exposure on the immunoglobulin production were not observed. The present study provides experimental evidence that daily inhalation of DE can enhance the allergen-induced respiratory disease such as allergic asthma. This effect may be mediated mainly by the enhanced local expression of IL-5 and GM-CSF. Less

我们研究了长期暴露于柴油机尾气（DE）、卵清蛋白（OA）或两者联合处理的气道组织病理学变化。并探讨了气道组织病理学改变与肺内免疫球蛋白生成及局部细胞因子水平的关系。将ICR小鼠暴露于清洁空气或DE中，烟尘浓度为0.3，1.0或3.0 mg/m2/d 13 mg/d 1，持续34或40周。暴露于DE 15周后，用10 μg OA腹腔内致敏小鼠，并在暴露的最后18或24周期间以3周间隔用1% OA气雾剂攻击。暴露于DE 34周导致典型变化的剂量依赖性增加，如气道中的非纤毛细胞增殖和上皮细胞肥大，但对支气管上皮中的杯状细胞增殖和气道中的嗜酸性粒细胞募集没有影响。OA刺激引起杯状细胞增殖和嗜酸性粒细胞反应的轻微变化， ...更多信息 很粗鲁除了DE诱导的典型变化进一步增加外，OA和DE联合暴露于3.0 mg/mイD13 D1还导致杯状细胞和嗜酸性粒细胞的变化增加。“以3.0 mg/m2的剂量暴露于DE D13-D1 40周也增强了过敏原诱导的嗜酸性粒细胞向气道粘膜下层的募集，并增加了肺中GM-CSF和IL-5的蛋白水平。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和气道对吸入乙酰胆碱的高反应性。OA治疗诱导OA特异性IgG 1和IgE在血浆中的生产，而DE暴露对免疫球蛋白生产的辅助作用没有观察到。本研究提供了实验证据，证明每天吸入DE可以增强过敏原诱导的呼吸道疾病，例如过敏性哮喘。这种作用可能主要通过增强局部IL-5和GM-CSF的表达来介导。少

项目成果

Takemichi Ichinose et al: "Long-term exposure todiesel exhaust enhances antigen-induced eossinophilic inflamation and epithelial damage in murin airway"Toxicological Sci. 44. 70-79 (1998)

Takemichi Ichinose 等人：“长期暴露于柴油尾气会增强鼠气道中抗原诱导的嗜酸性粒细胞炎症和上皮损伤”Toxicological Sci.

Takamichi Ichinose, Hirohisa Takano, Yuichi Miyabara and Masaru Sagai: "Long-term exposure to diesel exhaust enhances antigen-induced eoshinophilic inflammation and epithelia damage in murine airway"Toxicological Sci. 44. 70-79 (1998)

Takamichi Ichinose、Hirohisa Takano、Yuichi Miyabara 和 Masaru Sagai：“长期暴露于柴油废气会增强小鼠气道中抗原诱导的嗜酸性粒细胞炎症和上皮细胞损伤”毒理学科学。

Takamichi Ichinose et al.: "Long-term exposure to diesel exhaust enhances antigen-induced eosinophilic inflammation and epithelial damage in murin airway"Toxicological Sci,. 44. 70-79 (1998)

Takamichi Ichinose 等人：“长期暴露于柴油机尾气会增强小鼠气道中抗原诱导的嗜酸性粒细胞炎症和上皮损伤”Toxicological Sci,.