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杜氏响尾蛇毒液主要毒素(响尾蛇毒素)的免疫抑制作用。

Immunosuppresive role of principal toxin (crotoxin) of Crotalus durissus terrificus venom.

作者信息

Rangel-Santos A, Lima C, Lopes-Ferreira M, Cardoso D F

机构信息

Laboratory of Immunopathology, Butantan Institute Av. Vital Brazil, 1500. Butantan 05503-009 São Paulo, Brazil.

出版信息

Toxicon. 2004 Nov;44(6):609-16. doi: 10.1016/j.toxicon.2004.07.004.

DOI:10.1016/j.toxicon.2004.07.004
PMID:15501286
Abstract

The composition of the crotalic venom and the immunochemistry and/or pathophysiological characterization and main components were well studied. However, few studies have been carried out to investigate the effect of toxins of this venom on the development of the immune response. The objective of this work was to find out if venom or crotoxin of Crotalus durissus terrificus was able to modulate the immune response through its ability to change the mediators involved in the immune response by an unrelated antigen. We observed in the murine model, that venom as well as crotoxin have inhibitory effect on splenic cells proliferation induced by Con-A. Moreover, CB did not inhibit the proliferative response, suggesting that the integrity of crotoxin complex is necessary for the development of this phenomenon. Moreover, we showed that the effect on cellular proliferation was unrelated to cytotoxicity activity. We also observed that venom or crotoxin inhibited cytokine release induced in HSA immunised mice, mainly IL-2, IL-4 and IL-10, however, crotoxin did not inhibit the release of IFN-gamma. The involvement of T or B cells in the suppressive effect of venom was evaluated through the transference of purified splenic cells from venom-mice to normal mice that also produced low IgG1 anti-HSA levels, indicating the participation of these cells in this process. Mechanism of action of the crotalic venom on development of immune response to an unrelated antigen is much more complex, therefore it must not only involve the interaction of distinct cellular populations, but activation or inhibition of signalling proteins, need to be further investigated.

摘要

对响尾蛇毒液的成分、免疫化学和/或病理生理学特征及其主要成分都进行了充分研究。然而,针对这种毒液的毒素对免疫反应发展的影响开展的研究却很少。本研究的目的是确定巴西矛头蝮的毒液或响尾蛇毒素是否能够通过改变参与免疫反应的介质来调节免疫反应,这些介质由不相关抗原引发。我们在小鼠模型中观察到,毒液以及响尾蛇毒素对刀豆蛋白A诱导的脾细胞增殖具有抑制作用。此外,CB并未抑制增殖反应,这表明响尾蛇毒素复合物的完整性对于该现象的发生是必要的。此外,我们还表明对细胞增殖的影响与细胞毒性活性无关。我们还观察到,毒液或响尾蛇毒素抑制了在人血清白蛋白免疫小鼠中诱导的细胞因子释放,主要是白细胞介素-2、白细胞介素-4和白细胞介素-10,然而,响尾蛇毒素并未抑制干扰素-γ的释放。通过将来自接触毒液小鼠的纯化脾细胞转移到同样产生低水平抗人血清白蛋白IgG1的正常小鼠体内,评估了T细胞或B细胞在毒液抑制作用中的参与情况,这表明这些细胞参与了这一过程。响尾蛇毒液对不相关抗原免疫反应发展的作用机制要复杂得多,因此它不仅必须涉及不同细胞群体的相互作用,还涉及信号蛋白的激活或抑制,这需要进一步研究。

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