A murine model of IgE-mediated cow's milk hypersensitivity
A murine model of IgE-mediated cow's milk hypersensitivity
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DOI：
10.1016/s0091-6749(99)70492-6
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发表时间：
1999-02-01
影响因子：
14.2
通讯作者：
Sampson, HA
中科院分区：
文献类型：
--
作者：
Li, XM;Schofield, BH;Sampson, HA
背景：牛奶过敏（CMA）是儿童食物过敏的主要原因之一。由于缺乏合适的动物模型，对CMA发展的机制的理解一直受到阻碍。目的：我们试图建立一种ige介导的牛奶超敏反应（CMH）的小鼠模型，以模仿人类直接CMA的临床特征。方法：以3周龄C3H/HeJ小鼠为研究对象，采用加霍乱毒素的牛奶灌胃致敏方法，每周灌胃5次。结果：初饲后第3周，Chi特异性IgE抗体水平显著升高，在第6周达到峰值，第6周灌胃引起全身过敏反应并伴有血管渗漏，血浆组胺明显升高，肠道对酪蛋白的通透性增加，肠组织组织学检查显示明显的血管充血、水肿和肠细胞脱落。免疫血清热灭活消除被动皮肤过敏反应，证实了IgE介导CMH的作用。在该模型中，ige介导的CMH的发展可能是T-H2细胞介导的，因为对CM过敏的小鼠脾细胞的体外刺激诱导IL-4和IL-5水平显著升高，但ifn - γ没有显著升高。结论：该模型可为评估CMA的免疫致病机制和探索新的治疗方法提供有用的工具。
Background: Cow's milk allergy (CMA) is one of the leading causes of food allergy in children. Understanding the mechanisms involved in the development of CMA has been hampered by the lack of suitable animal models.Objective: We sought to develop a mouse model of IgE-mediated cow's milk hypersensitivity (CMH) that mimics the clinical features of immediate CMA in humans.Methods: Three-week-old C3H/HeJ mice were sensitized by intragastric administration of cow's milk (CM) plus cholera toxin and boosted 5 times at weekly intervals.Results: Chi-specific IgE antibody levels were significantly increased at 3 weeks and peaked at 6 weeks after the initial feeding, Intragastric challenge with Chi at week 6 elicited systemic anaphylaxis accompanied by vascular leakage, significantly increased plasma histamine, and increased intestinal permeability to casein, Histologic examination of intestinal tissue revealed marked vascular congestion, edema, and sloughing of enterocytes. The role of IgE in mediating CMH was confirmed by abrogation of passive cutaneous anaphylaxis reactions by heat inactivation of immune sera. Development of IgE-mediated CMH in this model is likely to be T-H2 cell mediated because in vitro stimulation of spleen cells from mice allergic to CM induced significant increases in the levels of IL-4 and IL-5, but not IFN-gamma.Conclusion: This model should provide a useful tool for evaluating the immunopathogenic mechanisms involved in CMA and for exploring new therapeutic approaches.