...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IDENTIFICATION OF THE GALACTOSE-ADHERENCE LECTIN EPITOPES OF ENTAMOEBA HISTOLYTICA THAT STIMULATE TUMOR NECROSIS FACTOR-ALPHA PRODUCTION BY MACROPHAGES
【24h】

IDENTIFICATION OF THE GALACTOSE-ADHERENCE LECTIN EPITOPES OF ENTAMOEBA HISTOLYTICA THAT STIMULATE TUMOR NECROSIS FACTOR-ALPHA PRODUCTION BY MACROPHAGES

机译:鉴定通过巨噬细胞刺激肿瘤坏死因子-α生产的恩氏单胞菌组织半乳糖粘附性卵磷脂表位

获取原文
获取原文并翻译 | 示例
           

摘要

The 170-kDa subunit of the galactose-adherence lectin (Gal-lectin) of Entamoeba histolytica mediates adherence to human colonic mucins and intestinal epithelium as a prerequisite to amebic invasion. The Gal-lectin is an immunodominant molecule and a protective antigen in the gerbil model of amebiasis. Tumor necrosis factor alpha (TNF-alpha) produced by activated macrophages enhances nitric oxide-dependent cytotoxicity in host defense against E. histolytica. The purpose of this study was to identify the Gal-lectin epitopes which stimulate TNF-alpha production by macrophages. Murine bone marrow-derived macrophages (BMMs) exposed to Gal-lectin (100-500 ng/ml) stimulated stable expression of TNF-alpha mRNA (8-fold increase) and TNF-alpha production similar to that of lipopolysaccharide-stimulated cells (100 ng/ml). Polyclonal anti-lectin serum specifically inhibited TNF-alpha mRNA induction in response to the Gal-lectin but not to lipopolysaccharide. Anti-lectin monoclonal antibodies 8C12, H85 and 1G7, which recognize nonoverlapping epitopes of the cysteine-rich region of the 170-kDa heavy subunit, inhibited both amebic adherence to mammalian cells and Gal-lectin-stimulated TNF-alpha mRNA expression by BMMs, but monoclonal antibody 7F4 did neither. As these inhibitory antibodies map to amino acids 596-1082 of the 170-kDa Gal-lectin, our results have identified the functional region that mediates amebic adherence and TNF-alpha mRNA induction in BMMs; thus, this region of the Gal-lectin is a subunit vaccine candidate.
机译:溶血变形杆菌的半乳糖粘附凝集素(Gal-lectin)的170 kDa亚基介导了对人类结肠粘蛋白和肠上皮的粘附,这是阿米巴侵袭的先决条件。 Gal-lectin在阿米巴病的沙鼠模型中是一种免疫优势分子和一种保护性抗原。活化的巨噬细胞产生的肿瘤坏死因子α(TNF-α)增强了宿主抗组织溶性大肠杆菌的一氧化氮依赖性细胞毒性。本研究的目的是鉴定刺激巨噬细胞刺激TNF-α产生的Gal-lectin表位。暴露于Gal-lectin(100-500 ng / ml)的鼠骨髓来源的巨噬细胞(BMM)刺激了TNF-αmRNA的稳定表达(增加了8倍)和TNF-α的产生,类似于脂多糖刺激的细胞( 100 ng / ml)。多克隆抗凝集素血清特异性地响应于Gal-lectin而不是脂多糖抑制TNF-αmRNA的诱导。抗凝集素单克隆抗体8C12,H85和1G7能够识别170 kDa重亚基富含半胱氨酸的区域的非重叠表位,既能抑制阿米巴对哺乳动物细胞的依从性,又能抑制BMMs对Gal-lectin刺激的TNF-αmRNA表达,但是单克隆抗体7F4却没有。由于这些抑制性抗体定位于170 kDa Gal-lectin的氨基酸596-1082,因此我们的结果已经确定了介导BMM中阿米巴粘附和TNF-αmRNA诱导的功能区域。因此,Gal-lectin的这一区域是候选的亚单位疫苗。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号