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学科主题: 药学
题名:
Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis
作者: Yan, TingTing1; Li, Qing2; Zhou, HuiTing1; Zhao, YueTao2; Yu, ShuQin1; Xu, GuangLin1; Yin, ZhiMin1; Li, ZhongJun2; Zhao, ZhiHui1
刊名: PLOS ONE
发表日期: 2012-02-02
DOI: 10.1371/journal.pone.0030110
卷: 7, 期:2
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
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
项目资助者: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55760
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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).
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