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。
Objective： To ascertain whether the immune complexes（ ICs） formed by Dengue virus 1 non-structure protein 1（ DENV1 NS1） and its Ig G antibodies could mediate passive systemic anaphylaxis（ PSA） and to explain the pathogenesis of Dengue hemorrhagic fever or Dengue shock syndrome（ DHF / DSS）. Methods： The monoclonal antibodies（ m Abs） or m Ab cocktails from 20 Ig G m Abs of DENV1 NS1 prepared in this lab were screened to initiate PSA and passive cutaneous anaphylaxis（ PCA） in mice. Meanwhile,the effects of Gd Cl3 and platelet activating factor（ PAF） antagonist CV-3988 on PSA induced by the NS1-Ig G ICs were observed. Results： Two groups of monoclonal antibody cocktails with purified NS1 were proved to be capable of provoking PCA and PSA in mice,whereas the other m Abs or m Ab cocktails could be not. The murine PSA initiated by NS1-Ig G（ 5D25＋3B1） ICs could be significantly inhibited by in vivo treatment with Gd Cl3 or PAF antagonist CV-3988. Conclusion： The NS1-Ig G ICs formed with DENV1NS1 and Ig G m Ab cocktails can mediate PSA and PCA,but not all of ICs formed by DENV1 NS1 m Abs or m Ab cocktails with DENV1NS1 can induce PSA,indicating that it may be related to the special epitopes of DENV1 NS1. The monocyte / macrophages and PAF may be as major effector cells and the major mediator for PSA induced by NS1-Ig G ICs,respectively.
作者
郭勇晖
朱伟
王艳芳
丁细霞
陈政良
富宁
GUO Yong-Hui ZHU Wei WANG Yah-Fang DING Xi-Xia CHEN Zheng-Liang FU Ning(Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2017年第3期338-342,共5页
Chinese Journal of Immunology
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)
