Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction
Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction
复制标题
Leukadherin-1 介导的 CD11b 激活抑制巨噬细胞中 LPS 诱导的促炎反应，并通过阻断 LPS-TLR4 相互作用保护小鼠免受内毒素休克
DOI：
10.3389/fimmu.2019.00215
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发表时间：
2019-02
影响因子：
7.3
通讯作者：
Si Chuanping
中科院分区：
文献类型：
--
作者：
Yao Xiaoying;Dong Guanjun;Zhu Yuzhen;Yan Fenglian;Zhang Hui;Ma Qun;Fu Xingqin;Li Xuehui;Zhang QingQing;Zhang Junfeng;Shi Hui;Ning Zhaochen;Dai Jun;Li Zhihua;Li Chunxia;Wang Bo;Ming Jiankuo;Yang Yonghong;Hong Feng;Meng Xiangzhi;Xiong Huabao;Si Chuanping
巨噬细胞的失调已被证明会导致异常的免疫反应和炎症性疾病。在巨噬细胞上表达的CD11b在调节病原体识别、吞噬作用和细胞存活方面起着关键作用。在……（“pres”可能是未完整输入的单词，如“present”等）
Dysregulation of macrophage has been demonstrated to contribute to aberrant immune responses and inflammatory diseases. CD11b, expressed on macrophages, plays a critical role in regulating pathogen recognition, phagocytosis, and cell survival. In the present study, we explored the effect of leukadherin-1 (LA1), an agonist of CD11b, on regulating LPS-induced pro-inflammatory response in macrophages and endotoxic shock. Intriguingly, we found that LA1 could significantly reduce mortalities of mice and alleviated pathological injury of liver and lung in endotoxic shock. In vivo studies showed that LA1-induced activation of CD11b significantly inhibited the LPS-induced pro-inflammatory response in macrophages of mice. Moreover, LA1-induced activation of CD11b significantly inhibited LPS/IFN-γ-induced pro-inflammatory response in macrophages by inhibiting MAPKs and NF-κB signaling pathways in vitro. Furthermore, the mice injected with LA1-treated BMDMs showed fewer pathological lesions than those injected with vehicle-treated BMDMs in endotoxic shock. In addition, we found that activation of TLR4 by LPS could endocytose CD11b and activation of CD11b by LA1 could endocytose TLR4 in vitro and in vivo, subsequently blocking the binding of LPS with TLR4. Based on these findings, we concluded that LA1-induced activation of CD11b negatively regulates LPS-induced pro-inflammatory response in macrophages and subsequently protects mice from endotoxin shock by partially blocking LPS-TLR4 interaction. Our study provides a new insight into the role of CD11b in the pathogenesis of inflammatory diseases.
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DOI：
10.4049/jimmunol.1403133
发表时间：
2015-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ghosh M;Subramani J;Rahman MM;Shapiro LH
通讯作者：
Shapiro LH
影响因子：
5.8
作者：
Jimenez-Garcia, Lidia;Angeles Higueras, Maria;Hortelano, Sonsoles
通讯作者：
Hortelano, Sonsoles
分枝杆菌酚类糖脂在巨噬细胞中选择性禁用TRIF依赖性TLR4信号。
影响因子：
7.3
作者：
Oldenburg R;Mayau V;Prandi J;Arbues A;Astarie-Dequeker C;Guilhot C;Werts C;Winter N;Demangel C
通讯作者：
Demangel C
影响因子：
4.4
作者：
R. Ingalls;Brian G. Monks;R. Savedra;W. Christ;R. Delude;A. Medvedev;T. Espevik;D. Golenbock
通讯作者：
R. Ingalls;Brian G. Monks;R. Savedra;W. Christ;R. Delude;A. Medvedev;T. Espevik;D. Golenbock
败血症和败血性休克
DOI：
10.21019/pharmacotherapyfirst.septic-shock_overview
发表时间：
2017
期刊：
--
影响因子：
--
作者：
Rinita H. Acevedo
通讯作者：
Rinita H. Acevedo