Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model
Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model
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DOI：
10.1159/000486313
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Yang, Cui Lan
中科院分区：
文献类型：
--
作者：
Li, Kai;Huang, En Ping;Yang, Cui Lan
背景：特异性免疫治疗，包括Toll样受体2激动剂(TLR2)，已被证明可以预防过敏反应，并具有很高的免疫调节能力。方法：筛选与TLR2胞外区表位结合的新抗体TSP-2。免疫组织化学、免疫印迹和流式细胞仪检测抗体对树突状细胞的作用。观察TSP-2对卵白蛋白(OVA)诱导的小鼠哮喘模型的影响。该模型为一种气道高反应性(AHR)模型，采用全身体积描记法、EL ISA法检测BALF和血清中Th1/Th2细胞因子水平、CCK-8法检测淋巴细胞增殖反应。用流式细胞仪检测TSP-2对骨髓来源的树突状细胞(BMDCs)成熟的影响。结果：TSP-2在体内外均能促进树突状细胞成熟和淋巴细胞增殖。TSP-2对Th1/Th2细胞因子分泌的影响略强于Pam3CSK4。TSP-2抗体可降低过敏性哮喘患者的AHR和OVA特异性IgE水平。在OVA致敏和激发的哮喘模型中，TSP-2抗体还可以减少肺部炎症和降低白细胞数量。TSP-2抗体可增加OVA刺激的BMDCs的I-A、CD80、CD86和MHC-II水平。结论：这项研究确定了一种新的治疗AHR的策略，它使用了抗TLR2的抗体。这也为靶向TLR2控制过敏性哮喘提供了理论依据。(C)2018年S.Karger AG，巴塞尔
Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1(Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam3CSK4. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2. (C) 2018 S. Karger AG, Basel