Ichinose T, Takano H, Miyabara Y, Sagai M
Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Toxicol Sci. 1998 Jul;44(1):70-9. doi: 10.1006/toxs.1998.2459.
The histopathologic changes in the murine airway induced by long-term exposure to diesel exhaust (DE), ovalbumin (OA), or both were investigated. The relationship between the histopathologic appearances in the airway and immunoglobulin production or local cytokine levels in the lungs was also studied. ICR mice were exposed to clean air or DE at a soot concentrations of 0.3, 1.0, or 3.0 mg/m3 for 34 weeks. Fifteen weeks after exposure to DE, mice were sensitized intraperitoneally with 10 micrograms of OA and challenged by an aerosol of 1% OA six times at 3-week intervals during the last 18 weeks of the exposure. DE exposure caused a dose-dependent increase of nonciliated 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 submucosa of the airway. OA treatment induced very slight changes in goblet cell proliferation and eosinophil recruitment. The combination of OA and DE exposure produced dose-dependent increases of goblet cells and eosinophils, in addition to further increases of the typical changes induced by DE. OA treatment induced OA-specific IgG1 and IgE production in plasma, whereas the adjuvant effects of DE exposure on immunoglobulin production were not observed. Inhalation of DE led to increased levels of IL-5 protein in the lung at a soot concentration of 1.0 and 3.0 mg/m3 with OA, although these increases did not reach statistical significance. We conclude that the combination of antigen and chronic exposure to DE produces increased eosinophilic inflammation, and cell damage to the epithelium may depend on the degree of eosinophilic inflammation in the airway.
研究了长期暴露于柴油废气（DE）、卵清蛋白（OA）或两者共同作用下对小鼠气道的组织病理学变化。还研究了气道组织病理学表现与肺部免疫球蛋白产生或局部细胞因子水平之间的关系。将ICR小鼠暴露于清洁空气或浓度为0.3、1.0或3.0mg/m³的DE环境中34周。在暴露于DE15周后，用10微克OA对小鼠进行腹腔致敏，并在暴露的最后18周内每隔3周用1%OA气雾剂进行6次激发。DE暴露导致气道中非纤毛细胞增殖和上皮细胞肥大呈剂量依赖性增加，但对支气管上皮杯状细胞增殖和气道黏膜下层嗜酸性粒细胞募集无影响。OA处理引起杯状细胞增殖和嗜酸性粒细胞募集的变化非常轻微。OA和DE联合暴露除了使DE诱导的典型变化进一步增加外，还导致杯状细胞和嗜酸性粒细胞呈剂量依赖性增加。OA处理诱导血浆中产生OA特异性IgG1和IgE，而未观察到DE暴露对免疫球蛋白产生的佐剂效应。在与OA共同作用下，吸入浓度为1.0和3.0mg/m³的DE会导致肺中IL-5蛋白水平升高，尽管这些升高未达到统计学显著性。我们得出结论，抗原与长期暴露于DE的联合作用会导致嗜酸性炎症增加，上皮细胞损伤可能取决于气道中嗜酸性炎症的程度。
