...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Clinical and diagnostic laboratory immunology >Important Role of P-Selectin for Leukocyte Recruitment, Hepatocellular Injury, and Apoptosis in Endotoxemic Mice
【24h】

Important Role of P-Selectin for Leukocyte Recruitment, Hepatocellular Injury, and Apoptosis in Endotoxemic Mice

机译：P-选择素对内毒素血症小鼠白细胞募集，肝细胞损伤和细胞凋亡的重要作用

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

摘要

Leukocyte recruitment in the liver includes a two-step procedure in which selectin-dependent leukocyte rolling is a prerequisite for subsequent CD18-dependent leukocyte firm adhesion in postsinusoidal venules. However, the roles of the individual selectins in leukocyte rolling and adhesion, hepatocellular injury, and apoptosis remain elusive. Therefore, we examined the pathophysiological role of P-, E-, and L-selectin in male C57BL/6 mice challenged with lipopolysaccharide (LPS) and d-galactosamine (Gal) by use of intravital microscopy of the liver microcirculation. In control animals, administration of LPS-Gal provoked reproducible hepatic damage, including marked increases of leukocyte recruitment, liver enzymes, and hepatocyte apoptosis and reduced sinusoidal perfusion. Interestingly, pretreatment with an anti-P-selectin antibody (RB40.34) markedly reduced leukocyte rolling and firm adhesion by 65 and 71%, respectively. Moreover, interference with P-selectin function significantly improved sinusoidal perfusion and reduced the increase in liver enzymes by 49 to 84% in endotoxemic mice. Moreover, the activity of caspase-3 and the number of apoptotic hepatocytes were significantly reduced by 55 and 54%, respectively, in RB40.34-treated animals. In contrast, administration of an anti-E-selectin antibody (10E9.6) and an anti-L-selectin antibody (Mel-14) did not protect against endotoxin-induced leukocyte responses or hepatic injury. In conclusion, our novel findings document a principal role of P-selectin in mediating leukocyte rolling, a precondition to the subsequent firm adhesion of leukocytes in liver injury. Furthermore, our novel data demonstrate that inhibition of P-selectin function reduces hepatocellular injury and apoptosis, suggesting a causal relationship between leukocyte recruitment on one hand and hepatocellular injury and apoptosis on the other hand. Based on these findings, it is suggested that P-selectin may be an important therapeutic target in endotoxin-induced liver injury.
机译：肝脏中白细胞募集包括两个步骤，其中选择素依赖性白细胞滚动是随后CD18依赖性白细胞牢固粘附在窦后小静脉中的先决条件。然而，各个选择素在白细胞滚动和粘附，肝细胞损伤和凋亡中的作用仍然难以捉摸。因此，我们通过使用肝脏微循环的活体显微镜检查了雄性C57BL / 6小鼠中脂蛋白（LPS）和d-半乳糖胺（Gal）攻击后P-，E-和L-选择素的病理生理作用。在对照动物中，LPS-Gal的使用会引起可再现的肝损伤，包括白细胞募集，肝酶和肝细胞凋亡的明显增加以及正弦曲线灌注的减少。有趣的是，用抗P-选择素抗体（RB40.34）进行的预处理分别将白细胞滚动和牢固粘附分别降低了65％和71％。此外，对P-选择蛋白功能的干扰显着改善了内毒素血症小鼠的正弦灌注，并使肝酶的增加减少了49％至84％。此外，在用RB40.34治疗的动物中，caspase-3的活性和凋亡肝细胞的数量分别显着减少了55％和54％。相反，施用抗E-选择蛋白抗体（10E9.6）和抗L-选择蛋白抗体（Mel-14）不能抵抗内毒素诱导的白细胞反应或肝损伤。总之，我们的新发现证明了P-选择素在介导白细胞滚动中的主要作用，这是随后白细胞在肝损伤中牢固粘附的前提。此外，我们的新数据表明，抑制P-选择蛋白的功能可减少肝细胞损伤和细胞凋亡，提示一方面白细胞募集与另一方面肝细胞损伤和细胞凋亡之间存在因果关系。基于这些发现，表明P-选择蛋白可能是内毒素诱导的肝损伤的重要治疗靶标。

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