【摘要】：目的:明確登革病毒Ⅰ型(Dengue virus serotype 1,DENV1)非結(jié)構(gòu)蛋白1(Non-structure protein 1,NS1)與其Ig G型抗體的免疫復(fù)合物(Immune complexes,ICs)能否誘導(dǎo)機體產(chǎn)生被動系統(tǒng)性過敏反應(yīng)(Passive systmic anaphylaxis,PSA),為闡明登革出血熱與登革休克綜合征(DHF/DSS)的發(fā)病機制提供依據(jù)。方法:從本課題組現(xiàn)有的多株抗NS1單克隆抗體中,篩選能夠與純化NS1結(jié)合并形成免疫復(fù)合物進而誘導(dǎo)小鼠產(chǎn)生被動系統(tǒng)性過敏反應(yīng)(PSA)和被動皮膚過敏反應(yīng)(Passive cutaneous anaphylaxis,PCA)的單抗或單抗組合;并觀察體內(nèi)氯化釓(Gd Cl_3)和血小板活化因子受體(PAFR)拮抗劑CV-3988處理對PSA的影響。結(jié)果:用親和層析純化的DENV1 NS1,從本室制備的20株Ig G型抗DENV1 NS1單抗中僅篩選出2組單抗組合制備免疫復(fù)合物(NS1-Ig G ICs)能成功誘導(dǎo)小鼠的PCA和PSA反應(yīng),而其他抗體或抗體組合并無此反應(yīng);用Gd Cl_3抑制單核巨噬細胞或CV-3988阻斷PAFR處理可抑制或減輕小鼠PSA反應(yīng)。結(jié)論:DENV1 NS1結(jié)合兩個Ig G型單抗組合的免疫復(fù)合物可誘發(fā)PSA與PCA,但并非所有的抗NS1單抗或抗體組合與NS1結(jié)合都能誘發(fā)PSA,推測與識別表位不同有關(guān);初步證明DENV1 NS1-Ig G ICs誘發(fā)PSA的主要效應(yīng)細胞是巨噬細胞,主要效應(yīng)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.
【作者單位】： 南方醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院免疫教研室;南方醫(yī)科大學(xué)珠江醫(yī)院檢驗醫(yī)學(xué)部;
【基金】：國家自然科學(xué)基金委員會-廣東省人民政府聯(lián)合基金資助項目(U1132002)
【分類號】：R512.8

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