Department of Pollutants and Health, National Institute for Research and Safety, F-54519 Vandoeuvre-les-Nancy, France.
Toxicol Appl Pharmacol. 2012 Apr 15;260(2):95-104. doi: 10.1016/j.taap.2012.02.009. Epub 2012 Feb 21.
Identification of allergenic chemicals is an important occupational safety issue. While several methods exist to identify contact sensitizers, there is currently no validated model to predict the potential of chemicals to act as respiratory sensitizers. Previously, we reported that cytometry analysis of the local immune responses induced in mice dermally exposed to the respiratory sensitizer trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB 1%) could identify divergent expression of several immune parameters. The present study confirms, first, that IgE-positive B cells, MHC class II molecules, interleukin (IL)-2, IL-4 and IL-4Rα can differentiate the allergic reactions caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone). The second part of the study was designed to test the robustness of these markers when classing the weakly immunogenic chemicals most often encountered. Six respiratory allergens, including TMA (2.5%), five contact allergens, including DNCB (0.25%), and two irritants were compared at doses of equivalent immunogenicity. The results indicated that IL-4Rα and IL-2 can be reliably used to discriminate sensitizers. Respiratory sensitizers induced markedly higher IL-4Rα levels than contact allergens, while irritants had no effect on this parameter. Inversely, contact allergens tended to induce higher percentages of IL-2⁺CD8⁺ cells than respiratory allergens. In contrast, the markers MHC-II, IgE and IL-4 were not able to classify chemicals with low immunogenic potential. In conclusion, IL-4Rα and IL-2 have the potential to be used in classifying a variety of chemical allergens.
鉴定变应原化学品是职业安全的一个重要问题。虽然有几种方法可以鉴定接触致敏原,但目前还没有经过验证的模型来预测化学品作为呼吸道致敏原的潜力。我们之前曾报道过,对经皮暴露于呼吸道致敏原均苯四甲酸酐(TMA10%)和接触致敏原二硝基氯苯(DNCB1%)的小鼠进行局部免疫反应的细胞分析,可以鉴定出几种免疫参数的不同表达。本研究首先证实,IgE 阳性 B 细胞、MHC Ⅱ类分子、白细胞介素(IL)-2、IL-4 和 IL-4Rα 可以区分高剂量强呼吸道(TMA、邻苯二甲酸酐和甲苯二异氰酸酯)和接触致敏原(DNCB、二硝基氟苯和噁唑酮)引起的过敏反应。研究的第二部分旨在测试这些标记物在分类最常见的弱免疫原性化学品时的稳健性。比较了六种呼吸道过敏原,包括 TMA(2.5%),五种接触过敏原,包括 DNCB(0.25%),以及两种刺激物,它们的剂量具有等效的免疫原性。结果表明,IL-4Rα 和 IL-2 可用于可靠地区分致敏原。呼吸道致敏原诱导的 IL-4Rα 水平明显高于接触致敏原,而刺激物对该参数没有影响。相反,接触致敏原倾向于诱导更高百分比的 IL-2+CD8+细胞比呼吸道致敏原。相比之下,MHC-II、IgE 和 IL-4 标记物不能对低免疫原性化学品进行分类。总之,IL-4Rα 和 IL-2 有可能用于分类各种化学变应原。