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特定的蝎子毒素暴露可诱导人外周血单个核细胞释放细胞因子。

Selected scorpion toxin exposures induce cytokine release in human peripheral blood mononuclear cells.

作者信息

Corzo Gerardo, Espino-Solis Gerardo Pavel

机构信息

Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 61500, Mexico.

Baylor Institute For Immunology Research, 3410 Worth Street, Suite 600, Dallas, TX 75246, USA.

出版信息

Toxicon. 2017 Mar 1;127:56-62. doi: 10.1016/j.toxicon.2017.01.007. Epub 2017 Jan 11.

Abstract

A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx's) was performed in order to evaluate their effect on human immune cells. The ScTx's chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin). A Luminex multiplex analysis was performed in order to determine the amounts chemokines and cytokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12-p40, IL-13, interferon alpha (IFN-α), interferon gamma (IFN-γ), tumor necrosis factor alpha TNF-α, and interferon-inducible protein-10 (IP-10) secreted from human PBMCs exposed to these toxins. Although, the ScTx Cn5 is not lethal for mammals, it was able to induce the secretion of cytokines IL-1β, IL-6, and TNF-α, IL-10 and IP-10 in comparison to the lethal CssII, which was able to induce only IP-10 secretion. Discrepin also was able to induce only IP-10. Interestingly, only low amounts of interferons α and β were induced in the presence of the ScTx's assayed. In a synergic experiment, the combination of Discrepin and Cn5 displayed considerable reverse effects on induction of IL-1β, IL-6, IL-10 and TNF-α, but they had a slight synergic effect on IP-10 cytokine production in comparison with the single effect obtained with the Cn5 alone. Thus, the results obtained suggest that the profile of secreted cytokines promoted by ScTx Cn5 is highly related with a cytokine storm event, and also it suggests that the mammalian lethal neurotoxins are not solely responsible of the scorpion envenomation symptomatology.

摘要

为了评估所选蝎毒素(ScTx's)对人体免疫细胞的影响,我们对用这些毒素刺激的人外周血单个核细胞(PBMCs)进行了细胞因子筛选。本报告中选用的ScTx's是三种典型的钳蝎科蝎毒肽,一种对哺乳动物有致死作用的苏氏正钳蝎毒素II(CssII),另一种对昆虫和甲壳类动物有致死作用的墨西哥正钳蝎毒素5(Cn5),还有一种无致死作用的差异蒂氏蝎毒素(Discrepin)。进行了Luminex多重分析,以确定暴露于这些毒素的人PBMCs分泌的趋化因子和细胞因子IL-1β、IL-2、IL-4、IL-5、IL-6、IL-10、IL-12-p40、IL-13、α干扰素(IFN-α)、γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)和干扰素诱导蛋白10(IP-10)的量。尽管ScTx Cn5对哺乳动物无致死作用,但与具有致死性的CssII相比,它能够诱导细胞因子IL-1β、IL-6、TNF-α、IL-10和IP-10的分泌,而CssII仅能诱导IP-10的分泌。Discrepin也只能诱导IP-10。有趣的是,在所检测的ScTx's存在的情况下,仅诱导产生少量的α和β干扰素。在一项协同实验中,Discrepin和Cn5的组合对IL-1β、IL-6、IL-10和TNF-α的诱导显示出相当大的反向作用,但与单独使用Cn5获得的单一作用相比,它们对IP-10细胞因子的产生有轻微的协同作用。因此,所获得的结果表明,ScTx Cn5促进分泌的细胞因子谱与细胞因子风暴事件高度相关,也表明哺乳动物致死性神经毒素并非蝎螫伤症状的唯一原因。

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