• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cell Science >Activation of microglia reveals a non-proteolytic cytokine function for tissue plasminogen activator in the central nervous system.
【24h】

Activation of microglia reveals a non-proteolytic cytokine function for tissue plasminogen activator in the central nervous system.

机译：小胶质细胞的激活揭示了中枢神经系统中组织纤溶酶原激活物的非蛋白水解细胞因子功能。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Tissue plasminogen activator mediates excitotoxin-induced neurodegeneration and microglial activation in the mouse hippocampus. Here we show that tissue plasminogen activator (tPA) acts in a protease-independent manner to modulate the activation of microglia, the cells of the central nervous system with macrophage properties. Cultured microglia from tPA-deficient mice can phagocytose as efficiently as wild-type microglia. However, tPA-deficient microglia in mixed cortical cultures exhibit attenuated activation in response to lipopolysaccharide, as judged by morphological changes, increased expression of the activation marker F4/80 and the release of the pro-inflammatory cytokine tumor necrosis factor-(&agr;). When tPA is added to tPA deficient cortical cultures prior to endotoxin stimulation, microglial activation is restored to levels comparable to that observed in wild-type cells. Proteolytically-inactive tPA can also restore activation of tPA-deficient microglia in culture and in vivo. However, this inactive enzyme does not restore susceptibility of tPA-deficient hippocampal neurons to excitotoxin-mediated cell death. These results dissociate two different functions of tPA: inactive enzyme can mediate microglial activation, whereas proteolytically-competent protein also promotes neuronal degeneration. Thus tPA is identified as a new cytokine in the central nervous system.
机译：组织纤溶酶原激活剂介导小鼠海马中兴奋性毒素诱导的神经变性和小胶质细胞激活。在这里，我们显示组织纤溶酶原激活剂（tPA）以蛋白酶非依赖性的方式调节小胶质细胞的活化，小胶质细胞是具有巨噬细胞特性的中枢神经系统细胞。来自tPA缺陷型小鼠的培养的小胶质细胞可以像野生型小胶质细胞一样有效地吞噬细胞。然而，如形态变化，激活标记物F4 / 80的表达增加以及促炎性细胞因子肿瘤坏死因子-（α）的释放所判断，混合皮质培养物中tPA缺乏的小胶质细胞显示出对脂多糖的减弱的激活作用。 。当在内毒素刺激之前将tPA添加到tPA缺陷型皮质培养物中时，小胶质细胞的激活恢复到与野生型细胞中观察到的水平相当的水平。蛋白水解失活的tPA还可以在培养和体内恢复tPA缺陷型小胶质细胞的活化。但是，这种无活性的酶不能恢复tPA缺陷海马神经元对兴奋性毒素介导的细胞死亡的敏感性。这些结果分离了tPA的两种不同功能：失活​​的酶可以介导小胶质细胞的活化，而具有蛋白水解能力的蛋白质也可以促进神经元变性。因此，tPA被鉴定为中枢神经系统中的一种新的细胞因子。

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