Murine strain differences in airway inflammation induced by diesel exhaust and house dust mite allergen

柴油机尾气和屋尘螨过敏原引起的气道炎症的小鼠品系差异

• 批准号: 12680550
• 负责人: ICHINOSE Takamichi
• 金额: $ 1.73万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680550/
• 关键词: Diesel exhaust; Bronchial astma; Cytokines; Murin strain difference; Eosinophils; Goblet cells; IgE production; IgGI production; IgG1抗体

House dust mites have known to implicate the increase of asthma prevalence today. Three strains of mice (BALB/c, ICR, and C3H/He) were exposed to DE at-a soot concentration of 3.O mg/m^3 or cline air for 8 weeks. These mice injected intratracheally with 1 μ g of Der f four times at 2-week intervals during 8 weeks of the exposure. Histopathological changes in the murine airway, asthma relevant cytokines and chemokines in the lungs, and allergen-specific immunoglobulins in plasma were investigated. DE exposure caused non-ciliated cell proliferation and epithelial cell hypertrophy in the airway of the all strains, and showed very slight goblet cell proliferation in the bronchial epithelium and eosinophil recruitment in the airway of the C3H/He mice. Der f treatment exhibited the recruitment of eosinophils and proliferation of goblet cells in the airway of the three strains. The increasing order of magnitude of those was BALB/c < ICR < C3H/He mice. DE+Der f increased significantly the recruitment of eosinophils in the BALB/c and ICR mice, and increased goblet cell proliferation in the ICR mice compared with Der f treatment. However, these phathologic changes decreased in the case of the C3H/He mice. DE+Der f caused the additional increases of IL-5, eotaxin and RANTES, and synergistic increases of MCP-1 and MIP-1 a in the three strains. The increasing order of IL-5 and eotaxin in lung tissues and Der f-specific lgG1 in plasma by DE+Der f was BALB/c < ICR < C3H/He mice. The production levels of IL-5 in lung tissues corresponded to the manifestations of eosinophilic airway inflammation by DE and/or Der f treatment. The aggravating effect of DE exposure may be mediated mainly by the increase of local expression of IL-5, eotaxin. Antigen-specific lgG1 suggests to be an important immunoglobulin in the pathogenesis of allergic asthma and in the enhancement of DE.

人们已经知道，屋尘螨与当今哮喘患病率的增加有关。三种品系的小鼠(BALB/c、ICR和C3H/He)分别暴露于浓度为3.0 mg/m~3的DE或斜面空气中8周。在暴露的8周期间，这些小鼠气管内注射1μg的Der f，每隔2周四次。观察小鼠呼吸道组织病理学改变，肺组织中哮喘相关细胞因子和趋化因子的变化，以及血浆中变应原特异性免疫球蛋白。De暴露可引起所有品系小鼠呼吸道无纤毛细胞增殖和上皮细胞肥大，C3H/He小鼠气道上皮杯状细胞增殖和嗜酸性粒细胞聚集。DERF处理后，3株小鼠呼吸道嗜酸性粒细胞聚集，杯状细胞增殖。其大小依次为BALB/c&lt；ICR&lt；C3H/He小鼠。De+Der f可显著增加BALB/c和ICR小鼠嗜酸粒细胞的募集，促进ICR小鼠的杯状细胞增殖。然而，在C3H/He小鼠中，这些表型变化减少。De+Der f可引起IL-5、嗜酸性粒细胞趋化因子和RANTES的进一步增加，以及MCP-1和MIP-1 a的协同增加。DE+Der_f组小鼠肺组织中IL-5、嗜酸性粒细胞趋化因子和血浆Der_f特异性lgG_1的递增顺序为：BALB/c&lt；ICR&lt；C3H/He。肺组织中IL-5的产生水平与DE和/或DERF治疗后的嗜酸性气道炎的表现相一致。DE暴露的加重作用可能主要是通过增加局部IL-5、嗜酸性粒细胞趋化因子的表达来实现的。抗原特异性免疫球蛋白lgG1在过敏性哮喘的发病机制中可能是一种重要的免疫球蛋白。