Macrophages Promote Liver Repair after Monocrotaline-Induced Liver Injury Via SDF-1/CXCR4 Axis

Macrophages are critical players of liver repair after acute liver injury induced by chemicals. Monocrotaline (MCT)-induced liver injury is established as a model of sinusoidal obstruction syndrome; however, little is known about the process underlying liver repair after the injury. Maximal liver injury occurred at 48 h post-MCT treatment in C57BL/6 mice, followed by repair at 120 h post-treatment. Macrophages extensively accumulated to the injured regions of livers at 72 h, which was associated with decreased mRNA levels related to pro-inflammatory mediators and increased anti-inflammatory mediators. The levels of stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor type 4 (CXCR4) were upregulated during the repair phase. SDF-1 and CXCR4 were expressed in sinusoidal endothelial cells and infiltrated macrophages, respectively. Further, macrophages expressing CXCR4 were derived form the bone marrow. CXCR4 blockade suppressed liver repair after MCT treatment. Accumulation of macrophages did not differ between the treatments, though mRNA levels of pro-inflammatory mediators were increased in CXCR4 antagonist-treated mice. By contrast, SDF-1 treatment stimulated liver repair, which was associated with increased levels of anti-inflammatory mediators. Accumulation of macrophages through SDF-1/CXCR4 axis contributes to liver repair after MCT treatment.