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
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 leukadhe...
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Frontiers Media S.A.
2019-02-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00215/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoying Yao Xiaoying Yao Guanjun Dong Yuzhen Zhu Fenglian Yan Hui Zhang Qun Ma Xingqin Fu Xuehui Li QingQing Zhang Junfeng Zhang Hui Shi Zhaochen Ning Jun Dai Zhihua Li Chunxia Li Bo Wang Jiankuo Ming Yonghong Yang Feng Hong Xiangzhi Meng Huabao Xiong Chuanping Si |
spellingShingle |
Xiaoying Yao Xiaoying Yao Guanjun Dong Yuzhen Zhu Fenglian Yan Hui Zhang Qun Ma Xingqin Fu Xuehui Li QingQing Zhang Junfeng Zhang Hui Shi Zhaochen Ning Jun Dai Zhihua Li Chunxia Li Bo Wang Jiankuo Ming Yonghong Yang Feng Hong Xiangzhi Meng Huabao Xiong Chuanping Si 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 Frontiers in Immunology CD11b macrophage endotoxin shock TLR4 LPS leukadherin-1 (LA1) |
author_facet |
Xiaoying Yao Xiaoying Yao Guanjun Dong Yuzhen Zhu Fenglian Yan Hui Zhang Qun Ma Xingqin Fu Xuehui Li QingQing Zhang Junfeng Zhang Hui Shi Zhaochen Ning Jun Dai Zhihua Li Chunxia Li Bo Wang Jiankuo Ming Yonghong Yang Feng Hong Xiangzhi Meng Huabao Xiong Chuanping Si |
author_sort |
Xiaoying Yao |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-02-01 |
description |
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. |
topic |
CD11b macrophage endotoxin shock TLR4 LPS leukadherin-1 (LA1) |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00215/full |
work_keys_str_mv |
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doaj-4069320008be4c649ab1f3befa21c8532020-11-24T22:22:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00215414608Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 InteractionXiaoying Yao0Xiaoying Yao1Guanjun Dong2Yuzhen Zhu3Fenglian Yan4Hui Zhang5Qun Ma6Xingqin Fu7Xuehui Li8QingQing Zhang9Junfeng Zhang10Hui Shi11Zhaochen Ning12Jun Dai13Zhihua Li14Chunxia Li15Bo Wang16Jiankuo Ming17Yonghong Yang18Feng Hong19Xiangzhi Meng20Huabao Xiong21Chuanping Si22Institute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaSchool of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaDepartment of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong, ChinaDepartment of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong, ChinaDepartment of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United StatesDepartment of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY, United StatesInstitute of Immunology and Molecular Medicine, Jining Medical University, Shandong, ChinaDysregulation 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00215/fullCD11bmacrophageendotoxin shockTLR4LPSleukadherin-1 (LA1) |