Bovine β-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/hGM-CSF transgenic mice
Bovine β-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/hGM-CSF transgenic mice
复制标题
使用人源化 NOG hIL-3/hGM-CSF 转基因小鼠的牛 β-乳球蛋白诱导的被动全身过敏反应模型
DOI：
10.1093/intimm/dxaa067
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发表时间：
2020
影响因子：
4.4
通讯作者：
Simons Peter J
中科院分区：
文献类型：
--
作者：
Ito Ryoji;Katano Ikumi;Otsuka Iyo;Takahashi Takeshi;Suemizu Hiroshi;Ito Mamoru;Simons Peter J
食物过敏是一种常见的疾病，由摄入含有过敏原的食物引起，如牛奶，鸡蛋，花生和小麦。全身性过敏反应是一种严重的超敏过敏反应，由表面高亲和力IgE受体（Fcε-RI）与过敏原特异性IgE和过敏原交联后肥大细胞或嗜碱性粒细胞脱颗粒引起。在这项研究中，我们开发了一种新的人肥大细胞/嗜碱性粒细胞移植的小鼠模型，重现了由β-乳球蛋白（BLG）（牛奶中发现的一种主要过敏原）引发的全身过敏反应。将人CD 34+造血干细胞转移到NOG（非Tg）或NOG hIL-3/hGM-CSF转基因（Tg）小鼠中。14-16周后，将牛BLG特异性人IgE静脉内注射到人源化小鼠中，然后在1天后静脉内或口服牛BLG暴露。体温在Tg，但不是在非Tg，小鼠逐渐下降，在10分钟内，和80%的Tg小鼠在1小时内通过静脉内BLG暴露死亡。与非Tg小鼠相比，Tg小鼠的血清组胺水平和过敏反应评分显著增加。此外，这些过敏症状显着抑制肾上腺素治疗的Tg小鼠。因此，目前的NOG hIL-3/hGM-CSF Tg小鼠模型可用于开发用于治疗食物过敏的新型过敏反应药物，以及用于低变应原性广泛水解牛乳乳清蛋白基婴儿配方食品的安全性评估。
Food allergy is a common disease caused by intake of allergen-containing foods, such as milk, eggs, peanuts and wheat. Systemic anaphylaxis is a severe hypersensitive allergic reaction resulting from degranulation of mast cells or basophils after cross-linking of surface high-affinity IgE receptors (Fcε-RI) with allergen-specific IgE and allergens. In this study, we developed a novel human mast cell/basophil-engrafted mouse model that recapitulates systemic anaphylaxis triggered by β-lactoglobulin (BLG), a major allergen found in cow’s milk. Human CD34+hematopoietic stem cells were transferred into NOG (non-Tg) or NOG hIL-3/hGM-CSF transgenic (Tg) mice. After 14–16 weeks, bovine BLG-specific human IgE was intravenously injected into humanized mice, followed by intravenous or oral bovine BLG exposure 1 day later. Body temperature in Tg, but not in non-Tg, mice gradually decreased within 10 min, and 80% of Tg mice died within 1 h by intravenous BLG exposure. Serum histamine levels and anaphylaxis scores in Tg mice were markedly increased compared to non-Tg mice. Furthermore, these allergic symptoms were significantly inhibited by epinephrine treatment of the Tg mice. Therefore, the current NOG hIL-3/hGM-CSF Tg mouse model may be useful for development of novel anaphylaxis drugs for treatment of food allergies and for safety assessment of low-allergenicity extensively hydrolyzed cow’s milk whey protein-based infant formulas.