Schouten Bastiaan, van Esch Betty C A M, Hofman Gerard A, van den Elsen Lieke W J, Willemsen Linette E M, Garssen Johan
Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Int Arch Allergy Immunol. 2008;147(2):125-34. doi: 10.1159/000135699. Epub 2008 Jun 3.
Cow's milk allergy (CMA) is characterized by hypersensitivity against casein or whey, affecting 2.5% of young infants. The pathogenesis of CMA involves IgE as well as non-IgE-mediated reactions and clinical symptoms are found in the skin, lungs and gastrointestinal tract. In this study, local and systemic immunopathology was determined in whey- or casein-allergic mice.
Mice were orally sensitized with casein or whey using cholera toxin as an adjuvant. Serum immunoglobulins and the acute allergic skin reaction (ear swelling 1 h after intradermal allergen challenge) were determined to reveal systemic hypersensitivity. Furthermore, pathophysiological changes were assessed within the intestine.
An acute allergic skin reaction was induced in both whey- and casein-sensitized mice. In these mice, whey-specific IgE, IgG(1), IgG(2a) and casein-specific IgG(1) levels were found to be increased. In addition, the serum mouse mast cell protease-1 (mMCP-1) concentration was enhanced, reflecting mast cell degranulation. Indeed, the number of mMCP-1-positive mast cells within the colon was diminished in both whey- and casein-sensitized mice. Only in casein-sensitized mice isometric contraction of the colon was reduced, reflecting motility alterations.
Mice, orally sensitized against casein or whey, revealed an allergen-specific acute allergic skin reaction. In casein-sensitized mice, hypocontractility of the colon reflected pathophysiological changes within the intestine. Allergen-induced ear swelling and intestinal contractility changes are novel parameters in animal models of CMA which may add to the search for new therapeutic strategies to relieve symptoms of CMA.
牛奶蛋白过敏（CMA）的特征是对酪蛋白或乳清蛋白过敏，影响2.5%的幼儿。CMA的发病机制涉及IgE以及非IgE介导的反应，临床症状出现在皮肤、肺部和胃肠道。在本研究中，对乳清蛋白或酪蛋白过敏的小鼠进行了局部和全身免疫病理学检测。
使用霍乱毒素作为佐剂，对小鼠进行酪蛋白或乳清蛋白口服致敏。测定血清免疫球蛋白和急性过敏性皮肤反应（皮内注射过敏原激发1小时后耳部肿胀）以揭示全身超敏反应。此外，评估肠道内的病理生理变化。
乳清蛋白和酪蛋白致敏的小鼠均诱发了急性过敏性皮肤反应。在这些小鼠中，发现乳清蛋白特异性IgE、IgG(1)、IgG(2a)和酪蛋白特异性IgG(1)水平升高。此外，血清小鼠肥大细胞蛋白酶-1（mMCP-1）浓度升高，反映肥大细胞脱颗粒。实际上，乳清蛋白和酪蛋白致敏的小鼠结肠内mMCP-1阳性肥大细胞数量均减少。仅酪蛋白致敏的小鼠结肠等长收缩减少，反映了运动性改变。
经口服对酪蛋白或乳清蛋白致敏的小鼠出现了过敏原特异性急性过敏性皮肤反应。在酪蛋白致敏的小鼠中，结肠收缩力减弱反映了肠道内的病理生理变化。过敏原诱导的耳部肿胀和肠道收缩力变化是CMA动物模型中的新参数，可能有助于寻找缓解CMA症状的新治疗策略。
