IR@PKUHSC  > 北京大学药学院
学科主题药学
Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis
Yan, TingTing1; Li, Qing2; Zhou, HuiTing1; Zhao, YueTao2; Yu, ShuQin1; Xu, GuangLin1; Yin, ZhiMin1; Li, ZhongJun2; Zhao, ZhiHui1
刊名PLOS ONE
2012-02-02
DOI10.1371/journal.pone.0030110
7期:2
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者Natural Science Foundation of China ; State New Drug Innovation Plan ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) ; Natural Science Foundation of China ; State New Drug Innovation Plan ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]EARLY LACTATE CLEARANCE ; SEPTIC SHOCK ; MOLECULAR-MECHANISMS ; LEUKOCYTE ADHESION ; CECAL LIGATION ; MODEL ; INFLAMMATION ; ACTIVATION ; MORTALITY ; INTEGRIN
英文摘要

Background: Systemic leukocyte activation and disseminated leukocyte adhesion will impair the microcirculation and cause severe decrements in tissue perfusion and organ function in the process of severe sepsis. Gu-4, a lactosyl derivative, could selectively target CD11b to exert therapeutic effect in a rat model of severe burn shock. Here, we addressed whether Gu-4 could render protective effects on septic animals.

Methodology/Principal Findings: On a murine model of endotoxemia induced by lipopolysaccharide (LPS), we found that the median effective dose (ED50) of Gu-4 was 0.929 mg/kg. In vivo treatment of Gu-4 after LPS challenge prominently attenuated LPS-induced lung injury and decreased lactic acid level in lung tissue. Using the ED50 of Gu-4, we also demonstrated that Gu-4 treatment significantly improved the survival rate of animals underwent sepsis induced by cecal ligation and puncture. By adhesion and transwell migration assays, we found that Gu-4 treatment inhibited the adhesion and transendothelial migration of LPS-stimulated THP-1 cells. By flow cytometry and microscopy, we demonstrated that Gu-4 treatment inhibited the exposure of active I-domain and the cluster formation of CD11b on the LPS-stimulated polymorphonuclear leukocytes. Western blot analyses further revealed that Gu-4 treatment markedly inhibited the activation of spleen tyrosine kinase in LPS-stimulated THP-1 cells.

Conclusions/Significance: Gu-4 improves the survival of mice underwent endotoxemia and sepsis, our in vitro investigations indicate that the possible underlying mechanism might involve the modulations of the affinity and avidity of CD11b on the leukocyte. Our findings shed light on the potential use of Gu-4, an interacting compound to CD11b, in the treatment of sepsis and septic shock.

语种英语
所属项目编号2008104GZ40166 ; 2009ZX09103-044
资助者Natural Science Foundation of China ; State New Drug Innovation Plan ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) ; Natural Science Foundation of China ; State New Drug Innovation Plan ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
WOS记录号WOS:000301979000002
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55760
专题北京大学药学院
作者单位1.Nanjing Normal Univ, Coll Life Sci, Jiangsu Prov Key Lab Mol & Med Biotechnol, Nanjing, Jiangsu, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Yan, TingTing,Li, Qing,Zhou, HuiTing,et al. Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis[J]. PLOS ONE,2012,7(2).
APA Yan, TingTing.,Li, Qing.,Zhou, HuiTing.,Zhao, YueTao.,Yu, ShuQin.,...&Zhao, ZhiHui.(2012).Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis.PLOS ONE,7(2).
MLA Yan, TingTing,et al."Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis".PLOS ONE 7.2(2012).
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Yan, TingTing]的文章
[Li, Qing]的文章
[Zhou, HuiTing]的文章
百度学术
百度学术中相似的文章
[Yan, TingTing]的文章
[Li, Qing]的文章
[Zhou, HuiTing]的文章
必应学术
必应学术中相似的文章
[Yan, TingTing]的文章
[Li, Qing]的文章
[Zhou, HuiTing]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。