CCR2 dependent neutrophil activation and mobilization rely on TLR4-p38 axis during liver ischemia-reperfusion injury.

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.