de Jonge Jonathan D, Knippels Léon M J, Ezendam Janine, Odink Jennie, Penninks André H, van Loveren Henk
University Maastricht, Department of Health Risk Analysis and Toxicology, Universiteitssingel 50, Postbus 616, 6200 MD Maastricht, Maastricht, The Netherlands.
Methods. 2007 Jan;41(1):99-111. doi: 10.1016/j.ymeth.2006.09.004.
This report describes the further development of a peanut allergy model in Brown Norway (BN) rats and in particular the importance of allergen-free breeding of the laboratory animals for the allergen to be used. For this purpose BN rats were bred for 3 generations on soy- and peanut-free feed since it is known that the legumes peanut and soy are cross-reactive. In addition, the effect of cholera toxin (CT), an oral adjuvant often used to increase the sensitivity of food allergy models, was investigated in the BN rat model. BN rats that were bred on both soy- and peanut-free feed could be sensitized orally to peanut (all exposed rats developed peanut-specific IgE, IgG2a and IgG1) and the adjuvant CT could only enhance this sensitization to a limited extent. We also found different protein recognition patterns against purified peanut allergens (Ara h1, Ara h2 and Ara h3) between intraperitoneally (i.p.) and orally sensitized BN rats. Orally sensitized rats recognized all tested allergens whereas i.p. sensitized rats only recognized Ara h1 and Ara h2. Our conclusion is that a model for food allergy should preferably be (A) oral and (B) if possible without the use of adjuvantia. Our model in BN rats unites these preferred characteristics. In addition, we show the importance of dietary control when conducting oral sensitization studies. Special attention must be paid to unscheduled dietary pre-exposure of the animals to the protein under investigation to obtain optimal oral sensitization.
本报告描述了褐家鼠（BN大鼠）花生过敏模型的进一步发展，尤其强调了为所使用的变应原对实验动物进行无变应原饲养的重要性。为此，由于已知花生和大豆这两种豆类存在交叉反应性，BN大鼠在不含大豆和花生的饲料上繁殖了3代。此外，还在BN大鼠模型中研究了霍乱毒素（CT）的作用，霍乱毒素是一种常用于提高食物过敏模型敏感性的口服佐剂。在不含大豆和花生的饲料上饲养的BN大鼠可以通过口服对花生致敏（所有暴露的大鼠均产生了花生特异性IgE、IgG2a和IgG1），而佐剂CT只能在有限程度上增强这种致敏作用。我们还发现，腹腔内（i.p.）致敏和口服致敏的BN大鼠对纯化的花生变应原（Ara h1、Ara h2和Ara h3）存在不同的蛋白质识别模式。口服致敏的大鼠识别所有测试的变应原，而腹腔内致敏的大鼠只识别Ara h1和Ara h2。我们的结论是，食物过敏模型最好应具备（A）口服方式，以及（B）如有可能不使用佐剂。我们的BN大鼠模型具备这些理想特征。此外，我们展示了在进行口服致敏研究时饮食控制的重要性。必须特别注意避免动物在计划外饮食中预先接触所研究的蛋白质，以获得最佳的口服致敏效果。
