Steerenberg P A, Withagen C E T, Dormans J A M A, van Dalen W J, van Loveren H, Casee F R
Laboratory for Toxicology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
J Toxicol Environ Health A. 2003 Aug 8;66(15):1421-39. doi: 10.1080/15287390306415.
In the framework of an EU study entitled "Respiratory Allergy and Inflammation Due to Ambient Particles" (RAIAP), various collected particulate matter samples were to be tested for their adjuvant potency in two animal models of allergy. A pollen allergy model in the Brown Norway (BN) rat and an ovalbumin model in the BALB/c mouse were used in this study to compare the discriminatory value of these two models and to evaluate them for later studies of collected RAIAP-samples. Two different sources of diesel exhaust particles (DEP I and DEP II ), a residual oil fly ash source (ROFA), and two sources of ambient particles (Ottawa dust, EHC-93, and road tunnel dust, RTD) were tested. Rats were sensitized intratracheally with Timothy grass pollen (Phleum pratense, 200 microl, 10 mg/ml) on d 0, challenged on d 21, and examined on d 25. Mice were sensitized intranasally at d 0 and 14, challenged intranasally at d 35, 38, and 41 (50 microl, 0.4 mg ovalbumin/ml), and examined at d 42. Particulate matter (PM) was administered either during the sensitization phase only or during the sensitization and challenge phases (for mice only) or during the challenge phase only. In the pollen model, only DEP I, but not DEP II, ROFA, EHC-93, and RTD, stimulated the immunoglobulin (Ig) E and IgG1 response in serum to pollen allergens. In addition to this adjuvant effect noted, no other biomarkers in lung or bronchoalveolar lavage (BAL) revealed adjuvant activity in the pollen model. In the BAL of BN rats exposed to a combination of pollen and PM, the percentages of eosinophilic granulocytes were decreased compared to the BAL of BN rats immunized with pollen only. In the ovalbumin model, the IgE levels in serum were increased in mice after coexposure to ovalbumin and PM (including DEPI, DEPII, ROFA, EHC-93, and RTD) in the sensitization phase but not after coexposure during the challenge phase only. The inflammatory response was greater in the lung, predominantly the influx of eosinophilic granulocytes, as was observed by both histopathological examination and BAL analysis. In addition, BAL levels of inflammatory interleukin (IL)-4 were increased. Based on the IgE antibody response to ovalbumin, the ovalbumin model ranked the adjuvant capacity of the particles in the following order: RTD > ROFA > EHC-93 > DEPI > DEPII. In conclusion, the ovalbumin model is a sensitive system to detect adjuvant activity of airborne particles, whereas the pollen-induced allergy model in rat was less sensitive.
在一项名为“环境颗粒物导致的呼吸道过敏与炎症”（RAIAP）的欧盟研究框架内，要在两种过敏动物模型中测试各种收集到的颗粒物样本的佐剂效力。本研究使用了棕色挪威（BN）大鼠的花粉过敏模型和BALB/c小鼠的卵清蛋白模型，以比较这两种模型的鉴别价值，并对收集到的RAIAP样本进行后续研究评估。测试了两种不同来源的柴油尾气颗粒（DEP I和DEP II）、一种残油飞灰来源（ROFA）以及两种环境颗粒物来源（渥太华粉尘、EHC - 93和公路隧道粉尘、RTD）。大鼠在第0天经气管内用梯牧草花粉（猫尾草，200微升，10毫克/毫升）致敏，在第21天进行激发，并在第25天进行检查。小鼠在第0天和第14天经鼻致敏，在第35、38和41天经鼻激发（50微升，0.4毫克卵清蛋白/毫升），并在第42天进行检查。颗粒物（PM）仅在致敏阶段给予，或在致敏和激发阶段给予（仅针对小鼠），或仅在激发阶段给予。在花粉模型中，只有DEP I能刺激血清中针对花粉过敏原的免疫球蛋白（Ig）E和IgG1反应，而DEP II、ROFA、EHC - 93和RTD则不能。除了这种观察到的佐剂效应外，在花粉模型中，肺或支气管肺泡灌洗（BAL）中的其他生物标志物均未显示出佐剂活性。在暴露于花粉和PM组合的BN大鼠的BAL中，嗜酸性粒细胞的百分比与仅用花粉免疫的BN大鼠的BAL相比有所降低。在卵清蛋白模型中，在致敏阶段同时暴露于卵清蛋白和PM（包括DEP I、DEP II、ROFA、EHC - 93和RTD）后，小鼠血清中的IgE水平升高，但仅在激发阶段同时暴露后则未升高。通过组织病理学检查和BAL分析均观察到，肺中的炎症反应更大，主要是嗜酸性粒细胞的流入增加。此外，BAL中炎症白细胞介素（IL）-4水平升高。基于对卵清蛋白的IgE抗体反应，卵清蛋白模型对颗粒佐剂能力的排序如下：RTD > ROFA > EHC - 93 > DEP I > DEP II。总之，卵清蛋白模型是检测空气中颗粒佐剂活性 的敏感系统，而大鼠中的花粉诱导过敏模型则不太敏感。
