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Sm28GST 衍生肽对小鼠肝脾血吸虫病的影响评估:C 末端肽脂肽形式的意义

Evaluation of the effect of Sm28GST-derived peptides in murine hepatosplenic schistosomiasis: interest of the lipopeptidic form of the C-terminal peptide.

作者信息

Pancré V, Wolowczuk I, Bossus M, Gras-Masse H, Guerret S, Delanoye A, Capron A, Auriault C

机构信息

Laboratoire d'Immunologie cellulaire de l'interface hôte/parasite et de la pathogénèse parasitaire, CNRS URA 1854, Institut Pasteur, Lille, France.

出版信息

Mol Immunol. 1994 Nov;31(16):1247-56. doi: 10.1016/0161-5890(94)90075-2.

Abstract

Among the synthetic peptides derived from the 28-kDa Schistosoma mansoni glutathione S-transferase (Sm28GST), immunization with the C-terminal peptide comprising amino acid residues 190-211 induced a reduction in splenomegaly, in the number of hepatic eggs and in hepatic fibrosis in mice infected by Schistosoma mansoni. The absence of antibodies specific for the Sm28GST or for the 190-211 peptide observed in our conditions of immunization with this peptide argued in favour of the involvement of cellular-dependent mechanisms in the reduction in hepatic pathology. This was confirmed by the passive transfer of 190-211 peptide-specific T-cell enriched spleen cells which reproduced the protective effect conferred by immunization with the 190-211 peptide. These 190-211 peptide-specific cells produced little IL4 and high levels of IFN-gamma, a potent inhibitor of collagen synthesis. Furthermore, the use of a lipopeptidic form of the 190-211 peptide significantly improved the reduction in hepatic pathology obtained with the uncoupled peptide and induced a durable protective response. These results provide encouraging information for the possible use of synthetic peptides in the immunoprophylaxis of Schistosomiasis.

摘要

在源自28 kDa曼氏血吸虫谷胱甘肽S-转移酶(Sm28GST)的合成肽中,用包含氨基酸残基190 - 211的C末端肽进行免疫,可使感染曼氏血吸虫的小鼠的脾肿大、肝内虫卵数量及肝纤维化程度降低。在用该肽进行免疫的条件下,未观察到针对Sm28GST或190 - 211肽的特异性抗体,这表明细胞依赖性机制参与了肝脏病理变化的减轻。用富含190 - 211肽特异性T细胞的脾细胞进行被动转移,重现了用190 - 211肽免疫所赋予的保护作用,从而证实了这一点。这些190 - 211肽特异性细胞产生的白细胞介素4很少,而干扰素-γ水平很高,干扰素-γ是胶原合成的有效抑制剂。此外,使用190 - 211肽的脂肽形式可显著增强未偶联肽所带来的肝脏病理变化减轻效果,并诱导产生持久的保护反应。这些结果为合成肽在血吸虫病免疫预防中的可能应用提供了令人鼓舞的信息。

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