CCR2 dependent neutrophil activation and mobilization rely on TLR4-p38 axis during liver ischemia-reperfusion injury
CCR2 dependent neutrophil activation and mobilization rely on TLR4-p38 axis during liver ischemia-reperfusion injury
复制标题
肝脏缺血再灌注损伤期间 CCR2 依赖性中性粒细胞激活和动员依赖于 TLR4-p38 轴
DOI：
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发表时间：
2017
影响因子：
2.2
通讯作者：
Zhang Jinxiang
中科院分区：
文献类型：
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作者：
Xu Peng;Zhang Junbin;Wang Hui;Wang Guoliang;Wang Cong-Yi;Zhang Jinxiang
肝脏缺血再灌注损伤(IRI)是一种常见的临床问题，其中中性粒细胞募集是一个重要事件。我们先前的研究揭示了C-C基序趋化因子受体2(CCR2)在肝脏IRI中性粒细胞中的重要作用。本研究的目的是进一步探讨在这一病理生理过程中调节中性粒细胞CCR2表达变化的潜在机制。在此，我们发现TLR4消融减少了中性粒细胞从骨髓中的动员和随后在肝脏IRI中的渗透；中性粒细胞来源的CCR2的表达也受到抑制。此外，中性粒细胞的动员依赖于中性粒细胞中CCR2的表达，而中性粒细胞的表达又依赖于肝脏IRI期间TLR4-p38轴的激活。总之，中性粒细胞来源的CCR2的表达调节了中性粒细胞从骨髓到肝脏的动员和渗透，这需要在肝脏IRI期间激活TLR4-p38轴。
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.