IgG型抗登革病毒NS1抗体介导被动系统性过敏反应的研究
发布时间：2018-08-14 09:56
【摘要】：目的:明确登革病毒Ⅰ型(Dengue virus serotype 1,DENV1)非结构蛋白1(Non-structure protein 1,NS1)与其Ig G型抗体的免疫复合物(Immune complexes,ICs)能否诱导机体产生被动系统性过敏反应(Passive systmic anaphylaxis,PSA),为阐明登革出血热与登革休克综合征(DHF/DSS)的发病机制提供依据。方法:从本课题组现有的多株抗NS1单克隆抗体中,筛选能够与纯化NS1结合并形成免疫复合物进而诱导小鼠产生被动系统性过敏反应(PSA)和被动皮肤过敏反应(Passive cutaneous anaphylaxis,PCA)的单抗或单抗组合;并观察体内氯化钆(Gd Cl_3)和血小板活化因子受体(PAFR)拮抗剂CV-3988处理对PSA的影响。结果:用亲和层析纯化的DENV1 NS1,从本室制备的20株Ig G型抗DENV1 NS1单抗中仅筛选出2组单抗组合制备免疫复合物(NS1-Ig G ICs)能成功诱导小鼠的PCA和PSA反应,而其他抗体或抗体组合并无此反应;用Gd Cl_3抑制单核巨噬细胞或CV-3988阻断PAFR处理可抑制或减轻小鼠PSA反应。结论:DENV1 NS1结合两个Ig G型单抗组合的免疫复合物可诱发PSA与PCA,但并非所有的抗NS1单抗或抗体组合与NS1结合都能诱发PSA,推测与识别表位不同有关;初步证明DENV1 NS1-Ig G ICs诱发PSA的主要效应细胞是巨噬细胞,主要效应分子是PAF。
[Abstract]:Objective: to determine whether the Non-structure protein 1 NS1 (Non-structure protein 1 ns1) and the Immune complex of its IgG antibody can induce the passive systemic allergic reaction (Passive systmic anaphylaxis PSA), and to elucidate the relationship between dengue haemorrhagic fever (DHF) and dengue fever (DHF). To provide evidence for the pathogenesis of DHF/DSS. Methods: from the existing monoclonal antibodies against NS1 in our group, A combination of McAbs or McAbs that can bind to purified NS1 and form immune complexes to induce passive systemic allergic reaction (PSA) and passive skin allergic reaction (Passive cutaneous anaphylaxis PCA) in mice was screened. The effects of gadolinium chloride (Gd Cl_3) and platelet activating factor receptor (PAFR) antagonist CV-3988 on PSA were observed. Results: DENV1 NS1 was purified by affinity chromatography. Only two groups of McAbs were selected from 20 McAbs prepared in our laboratory. (NS1-Ig G ICs) can induce PCA and PSA reaction in mice successfully. Gd Cl_3 could inhibit mononuclear macrophages or block PAFR treatment with CV-3988, which could inhibit or attenuate the PSA reaction in mice. Conclusion the immune complexes of NS1 combined with two Ig G McAbs can induce PSA and PCA.However, not all anti NS1 McAbs or combinations of antibodies combined with NS1 can induce PSAs, which may be related to the identification of different epitopes. The main effector cells of PSA induced by DENV1 NS1-Ig G ICs were macrophages, and the main effector molecules were PAF.
【作者单位】： 南方医科大学基础医学院免疫教研室;南方医科大学珠江医院检验医学部;
【基金】：国家自然科学基金委员会-广东省人民政府联合基金资助项目(U1132002)
【分类号】：R512.8
本文编号：2182493
[Abstract]:Objective: to determine whether the Non-structure protein 1 NS1 (Non-structure protein 1 ns1) and the Immune complex of its IgG antibody can induce the passive systemic allergic reaction (Passive systmic anaphylaxis PSA), and to elucidate the relationship between dengue haemorrhagic fever (DHF) and dengue fever (DHF). To provide evidence for the pathogenesis of DHF/DSS. Methods: from the existing monoclonal antibodies against NS1 in our group, A combination of McAbs or McAbs that can bind to purified NS1 and form immune complexes to induce passive systemic allergic reaction (PSA) and passive skin allergic reaction (Passive cutaneous anaphylaxis PCA) in mice was screened. The effects of gadolinium chloride (Gd Cl_3) and platelet activating factor receptor (PAFR) antagonist CV-3988 on PSA were observed. Results: DENV1 NS1 was purified by affinity chromatography. Only two groups of McAbs were selected from 20 McAbs prepared in our laboratory. (NS1-Ig G ICs) can induce PCA and PSA reaction in mice successfully. Gd Cl_3 could inhibit mononuclear macrophages or block PAFR treatment with CV-3988, which could inhibit or attenuate the PSA reaction in mice. Conclusion the immune complexes of NS1 combined with two Ig G McAbs can induce PSA and PCA.However, not all anti NS1 McAbs or combinations of antibodies combined with NS1 can induce PSAs, which may be related to the identification of different epitopes. The main effector cells of PSA induced by DENV1 NS1-Ig G ICs were macrophages, and the main effector molecules were PAF.
【作者单位】： 南方医科大学基础医学院免疫教研室;南方医科大学珠江医院检验医学部;
【基金】：国家自然科学基金委员会-广东省人民政府联合基金资助项目(U1132002)
【分类号】：R512.8
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