Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation.
Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation.
复制标题
用于过敏性炎症功能分析的新型嗜碱性粒细胞或嗜酸性粒细胞缺失小鼠模型。
DOI：
10.1371/journal.pone.0060958
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yonekawa H
中科院分区：
文献类型：
--
作者：
Matsuoka K;Shitara H;Taya C;Kohno K;Kikkawa Y;Yonekawa H
嗜碱性粒细胞和嗜酸性粒细胞在各种宿主防御机制中发挥重要作用，但也作为过敏性疾病的有害效应物。我们产生了新的嗜碱性粒细胞和嗜酸性粒细胞耗竭小鼠模型，通过引入人白喉毒素（DT）受体基因的小鼠CD 203 c和嗜酸性粒细胞过氧化物酶启动子的控制下，分别研究这些细胞在免疫反应中的关键作用。这些小鼠在DT给药后表现出靶细胞的选择性耗竭。在嗜碱性粒细胞耗竭模型中，DT给药以剂量依赖性方式减弱IgG介导的全身过敏反应中的体温下降，并几乎完全消除IgE介导的慢性过敏性炎症（IgE-CAI）中耳肿胀的发展，这是一种典型的皮肤肿胀反应，伴有大量嗜酸性粒细胞浸润。相比之下，在嗜酸性粒细胞耗竭模型中，DT给药改善了IgE-CAI中的耳肿胀，无论DT是在抗原激发之前、同时还是之后给药，均具有显著较低数量的嗜酸性粒细胞浸润到肿胀部位。这些结果证实，嗜碱性粒细胞和嗜酸性粒细胞作为发起人和效应，分别在IgE-CAI。此外，抗体阵列分析表明，嗜酸性粒细胞趋化因子-2是吸引促炎细胞的主要趋化因子，导致慢性过敏性炎症。因此，本研究中建立的两种小鼠模型是研究嗜碱性粒细胞和嗜酸性粒细胞在体内作用的潜在有用和强大的工具。嗜碱性粒细胞和嗜酸性粒细胞耗竭小鼠模型的组合提供了一种新的方法来理解过敏性炎症的复杂机制，如特应性皮炎和哮喘。
Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT) receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI), a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the in vivo roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.
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影响因子：
32.4
作者：
Mukai, K;Matsuoka, K;Karasuyama, H
通讯作者：
Karasuyama, H
影响因子：
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作者：
Kojima, Toshiyuki;Obata, Kazushige;Karasuyama, Hajime
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Karasuyama, Hajime
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56.9
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Lee, DM;Friend, DS;Brenner, MB
通讯作者：
Brenner, MB
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作者：
Dombrowicz, D;Flamand, V;Kinet, JP
通讯作者：
Kinet, JP
影响因子：
20.3
作者：
Bühring, HJ;Seiffert, M;Sano, K
通讯作者：
Sano, K