• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Anthrax Edema Toxin Impairs Clearance in Mice
【24h】

Anthrax Edema Toxin Impairs Clearance in Mice

机译：炭疽水肿毒素损害小鼠的清除率

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

摘要

The anthrax edema toxin (ET) of Bacillus anthracis is composed of the receptor-binding component protective antigen (PA) and of the adenylyl cyclase catalytic moiety, edema factor (EF). Uptake of ET into cells raises intracellular concentrations of the secondary messenger cyclic AMP, thereby impairing or activating host cell functions. We report here on a new consequence of ET action in vivo. We show that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the presence of enzymatically active EF. These higher concentrations were not caused by ET-induced inhibition of PA endocytosis; on the contrary, ET induced increased PA binding and uptake of the PA oligomer in vitro and in vivo through upregulation of the PA receptors TEM8 and CMG2 in both myeloid and nonmyeloid cells. ET effects on protein clearance from circulation appeared to be global and were not limited to PA. ET also impaired the clearance of ovalbumin, green fluorescent protein, and EF itself, as well as the small molecule biotin when these molecules were coinjected with the toxin. Effects on injected protein levels were not a result of general increase in protein concentrations due to fluid loss. Functional markers for liver and kidney were altered in response to ET. Concomitantly, ET caused phosphorylation and activation of the aquaporin-2 water channel present in the principal cells of the collecting ducts of the kidneys that are responsible for fluid homeostasis. Our data suggest that in vivo, ET alters circulatory protein and small molecule pharmacokinetics by an as-yet-undefined mechanism, thereby potentially allowing a prolonged circulation of anthrax virulence factors such as EF during infection.
机译：炭疽杆菌的炭疽水肿毒素（ET）由受体结合​​成分保护性抗原（PA）和腺苷酸环化酶催化部分水肿因子（EF）组成。 ET被细胞吸收会增加次级信使环AMP的细胞内浓度，从而削弱或激活宿主细胞的功能。我们在这里报告ET作用体内的新结果。我们显示在毒性和感染的小鼠模型中，在存在酶促活性EF的情况下，血清PA浓度明显更高。这些较高的浓度不是由ET诱导的PA内吞作用的抑制引起的。相反，ET通过上调髓样和非髓样细胞中PA受体TEM8和CMG2的表达而增强了PA结合，并在体外和体内吸收了PA低聚物。 ET对循环蛋白清除的影响似乎是全局性的，并不限于PA。当这些分子与毒素共同注射时，ET还损害卵清蛋白，绿色荧光蛋白和EF本身以及小分子生物素的清除。对注射蛋白质水平的影响并不是由于液体流失而导致蛋白质浓度普遍增加的结果。肝和肾的功能标志物响应ET而改变。随之而来的是，ET引起了肾脏收集管主要细胞中存在的aquaporin-2水通道的磷酸化和活化，该通道负责液体体内稳态。我们的数据表明，体内 ET通过一种尚未定义的机制改变了循环蛋白和小分子药代动力学，从而潜在地延长了感染过程中诸如EF等炭疽毒力因子的循环。

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