在肝脏缺血再灌注损伤期间，CCR2依赖性中性粒细胞的激活和动员依赖于TLR4-p38轴。
CCR2 dependent neutrophil activation and mobilization rely on TLR4-p38 axis during liver ischemia-reperfusion injury.
作者信息
Xu Peng, Zhang Junbin, Wang Hui, Wang Guoliang, Wang Cong-Yi, Zhang Jinxiang
机构信息
Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430022, Hubei, China.
Department of Genetics, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China.
出版信息
Am J Transl Res. 2017 Jun 15;9(6):2878-2890. eCollection 2017.
Liver ischemia-reperfusion injury (IRI) is a common clinical problem in which neutrophil recruitment is an essential event. Our previous study revealed the important role of C-C motif chemokine receptor 2 (CCR2) in neutrophils during liver IRI. The aim of the present study was to further investigate the underlying mechanisms mediating the changes in CCR2 expression in neutrophils during this pathophysiological process. Herein, we found that TLR4 ablation reduced neutrophil mobilization from the bone marrow and the subsequent infiltration into the liver during liver IRI; neutrophil-derived CCR2 expression was also repressed. In addition, neutrophil mobilization was dependent on CCR2 expression in neutrophils, which in turn relied on activation of the TLR4-p38 axis during liver IRI. In conclusion, neutrophil-derived CCR2 expression regulates neutrophil mobilization from the bone marrow and infiltration into the liver, which requires activation of the TLR4-p38 axis during liver IRI.
肝脏缺血再灌注损伤（IRI）是一个常见的临床问题，其中中性粒细胞募集是一个关键事件。我们之前的研究揭示了C-C基序趋化因子受体2（CCR2）在肝脏IRI期间中性粒细胞中的重要作用。本研究的目的是进一步探究在此病理生理过程中介导中性粒细胞中CCR2表达变化的潜在机制。在此，我们发现Toll样受体4（TLR4）缺失减少了肝脏IRI期间中性粒细胞从骨髓的动员以及随后向肝脏的浸润；中性粒细胞来源的CCR2表达也受到抑制。此外，中性粒细胞的动员依赖于中性粒细胞中CCR2的表达，而这又依赖于肝脏IRI期间TLR4-p38轴的激活。总之，中性粒细胞来源的CCR2表达调节中性粒细胞从骨髓的动员和向肝脏的浸润，这需要肝脏IRI期间TLR4-p38轴的激活。
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