Steerenberg P A, van Dalen W J, Withagen C E T, Dormans J A M A, van Loveren H
Laboratory for Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
Inhal Toxicol. 2003 Nov;15(13):1309-25. doi: 10.1080/08958370390241786.
Epidemiological and experimental studies have not only shown that air pollution induces increased pulmonary morbidity, and mortality, but also that air pollution components may potentiate allergic responses. The respiratory allergy model to ovalbumin in the mouse has been shown a useful tool to characterize the adjuvant potency of air pollution components. However, the choice for the most effective route of administration for testing small amounts of air pollution component is hampered by the diversity of routes of administration used. To test the adjuvant activity of airborne particles (Ottawa dust EHC-93), we studied the optimal route of respiratory administration: intranasally (in) and aerosol (aero) in comparison with responses observed by intraperitoneal (ip) with diesel exhaust particles (DEP) as a positive control. Our results show that the combination of in/aero with ovalbumin caused almost similar immunoglobulin (Ig)E and inflammatory responses compared to the ip/aero. In/in application induced less responses for IgE, less inflammation in the lung, and less increased numbers of eosinophils in the bronchoalveolar lavage (BAL). This response increased dramatically when ovalbumin was coadministered with DEP. Subsequently, EHC-93, which is made up of airborne particles, was tested via the in/in route of administration. EHC-93 induced similar IgE responses, inflammation, and eosinophilic response in BAL compared to DEP. In addition, EHC-93 increased the airway responsiveness of the ovalbumin-sensitized mice measured in unrestrained condition and not in nonsensitized control mice. It is concluded that intranasal sensitization with intranasal challenge with airborne particles (EHC-93) is an effective route of administration to show potency of adjuvant activity of airborne particles.
流行病学和实验研究不仅表明空气污染会导致肺部发病率和死亡率上升，还表明空气污染成分可能会增强过敏反应。小鼠对卵清蛋白的呼吸道过敏模型已被证明是一种用于表征空气污染成分佐剂效力的有用工具。然而，由于使用的给药途径多种多样，选择最有效的给药途径来测试少量空气污染成分受到了阻碍。为了测试空气中颗粒物（渥太华粉尘EHC - 93）的佐剂活性，我们研究了呼吸道给药的最佳途径：鼻内（in）和气溶胶（aero）给药，并与腹腔内（ip）注射柴油尾气颗粒（DEP）作为阳性对照所观察到的反应进行比较。我们的结果表明，与ip/aero相比，in/aero与卵清蛋白联合使用引起的免疫球蛋白（Ig）E和炎症反应几乎相似。In/in给药诱导的IgE反应较少，肺部炎症较少，支气管肺泡灌洗（BAL）中嗜酸性粒细胞数量增加也较少。当卵清蛋白与DEP共同给药时，这种反应显著增加。随后，通过in/in给药途径测试了由空气中颗粒物组成的EHC - 93。与DEP相比，EHC - 93在BAL中诱导了相似的IgE反应、炎症反应和嗜酸性粒细胞反应。此外，EHC - 93增加了在无约束条件下测量的卵清蛋白致敏小鼠的气道反应性，而在未致敏的对照小鼠中则没有增加。结论是，用空气中颗粒物（EHC - 93）进行鼻内致敏和鼻内激发是显示空气中颗粒物佐剂活性效力的有效给药途径。
