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作 者:徐卫锋[1] 季永镛[1] 吴亚娣 林国妹 叶敏 孙兵[1]
机构地区:[1]中国科学院上海生命科学研究院生化细胞所分子免疫组,上海中国200031
出 处:《Acta Pharmacologica Sinica》2001年第8期736-740,共5页中国药理学报(英文版)
基 金:Project supported by 973 Project(G1999053907); the National Natural Science Foundation of China(No 39770695)
摘 要:AIM: To study the mechanism of trichosanthin (TCS)-induced ovalbumin (OVA)-specific immunoglobulin E (IgE) response in vivo. METHODS: To determine whether interleukin-4 (IL-4) was involved in TCS-induced IgE production, TCS and OVA co-immunized mice were treated with anti-IL-4 monoclonal antibodies (mAb) and OVA-specific serum IgE production was measured by enzyme-linked immunosorbent assay (ELISA). To distinguish whether recombinant IL-4 (rIL-4) was sufficient to support OVA-specific IgE response, OVA alone immunized mice were treated with rIL-4 and OVA-induced IgE production were examined by ELISA in the serum. To determine whether additional factors were involved in TCS-induced IgE response, the kinetic expression of CD40 ligand (CD40L), tumor necrosis factor-a (TNF-a), and interleukin-13 (IL-13) were measured by semi-quantitative RT-PCR in draining mesenteric lymph node (MLN) from TCS-immunized mice. RESULTS: TCS-induced OVA-specific IgE production was suppressed by anti-IL-4 antibody, whereas IL-4 alone could not induce OVA-specific IgE production. CD40L, TNF-a, and IL-13 all expressed high levels in MLN after both primary and secondary immune responses. Among them CD40L had the similar transient expression peak to that of IL-4. CONCLUSION: IL-4 was indispensable for TCS-induced OVA-specific IgE production, and the other three factors examined may alsobe involved in, but CD40L may play a more important role.目的:研究小鼠模型中天花粉蛋白(TCS)诱导的卵清白蛋白(OVA)特异性的E型免疫球蛋白(IgE)应答反应的可能机理。方法:首先用抗白介素-4(IL-4)的单抗治疗TCS和卵清白蛋白(OVA)免疫的小鼠,通过减少内源性IL-4的水平,以观察其对血清中IgE抗体水平的影响。其次,用重组IL-4处理小鼠,通过增加外源性IL-4的水平观察其对血清中OVA特异性IgE形成的影响。最后,我们在TCS免疫小鼠IgE形成过程中,用半定量PCR方法检测了腹腔淋巴结中CD40的配体(CD40L),肿瘤坏死因子-α(TNF-α)和白介素-13(IL-13)基因表达的趋势。结果:抗IL-4的单抗可以抑制TCS对OVA诱导的特异性IgE的形成,但重组IL-4本身并不能引起OVA特异的IgE应答反应。在TCS的初次和二次免疫中均有较高的表达峰,且CD40L的表达峰与IL-4类似,仅持续较短的时间。结论:IL-4对于TCS诱导的IgE应答反应为必要非充分条件。CD40L、TNF-α和IL-13可能也参与了此过程,其中CD40L可能具有与IL-4同样重要的作用。
关 键 词:TRICHOSANTHIN IMMUNOGLOBULINS inter-leukin-4 INTERLEUKIN-13 tumor necrosis factor ligands
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