• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >N-Linked Glycosylation Is Required for C1 Inhibitor-Mediated Protection from Endotoxin Shock in Mice
【24h】

N-Linked Glycosylation Is Required for C1 Inhibitor-Mediated Protection from Endotoxin Shock in Mice

机译：C抑制剂介导的小鼠内毒素休克所需要的N联糖基化。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

C1 inhibitor (C1INH) prevents endotoxin shock in mice via a direct interaction with lipopolysaccharide (LPS). This interaction requires the heavily glycosylated amino-terminal domain of C1INH. C1INH in which N-linked carbohydrate was removed by using N-glycosidase F was markedly less effective in protecting mice from LPS-induced lethal septic shock. N-deglycosylated C1INH also failed to suppress fluorescein isothiocyanate (FITC)-LPS binding to and LPS-induced tumor necrosis factor alpha mRNA expression by the murine macrophage-like cell line, RAW 264.7, and cells in human whole blood. In an enzyme linked immunosorbent assay, the N-deglycosylated C1INH bound to LPS very poorly. In addition, C1INH was shown to bind to diphosphoryl lipid A (dLPA) but only weakly to monophosphoryl lipid A (mLPA). As with intact LPS, binding of N-deglycosylated C1INH to dLPA and mLPA was diminished in comparison with the native protein. Removal of O-linked carbohydrate had no effect on any of these activities. Neither detoxified LPS, dLPA, nor mLPA had any effect on the rate or extent of C1INH complex formation with C1s or on cleavage of the reactive center loop by trypsin. These data demonstrate that N-linked glycosylation of C1INH is essential to mediate its interaction with the LPA moiety of LPS and to protect mice from endotoxin shock.
机译：C1抑制剂（C1INH）通过与脂多糖（LPS）的直接相互作用来预防小鼠的内毒素休克。这种相互作用需要C1INH的高度糖基化的氨基末端结构域。通过使用 N -糖苷酶F去除N-连接的碳水化合物的C1INH在保护小鼠免受LPS诱导的致死性败血性休克中的效力显着降低。 N-去糖基化的C1INH也无法抑制鼠巨噬细胞样细胞系RAW 264.7和人全血细胞中异硫氰酸荧光素（FITC）-LPS与LPS诱导的肿瘤坏死因子αmRNA表达的结合。在酶联免疫吸附测定中，N-去糖基化的C1INH与LPS的结合非常差。此外，C1INH已显示与二磷酰脂质A（dLPA）结合，但仅与单磷酰脂质A（mLPA）结合较弱。与完整的LPS一样，与天然蛋白相比，N-去糖基化的C1INH与dLPA和mLPA的结合减少。除去O-连接的碳水化合物对任何这些活性都没有影响。排毒的LPS，dLPA或mLPA均不影响C1INH与C1s形成复合物的速率或程度，也不影响胰蛋白酶对反应性中心环的切割。这些数据表明，C1INH的N-联糖基化对于介导其与LPS的LPA部分的相互作用以及保护小鼠免受内毒素休克至关重要。

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