Background: Liver regeneration following 70 % partial hepatectomy (PH) requires the coordinated expression of soluble mediators produced by macrophages. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulus of monocyte recruitment and macrophage activation. The goal of this study was to determine how MCP-1 contributes to liver regeneration.
Methods: PH was performed on anesthetized C57Bl/6 (wild type) and MCP-1 knockout mice, and macrophage-produced cytokines and hepatocyte proliferation were measured.
Results: In wild type mice, hepatic MCP-1 protein levels increased 4-6 h after PH, and elevated plasma MCP-1 levels were detected 12 h after PH. Hepatocyte proliferation was comparable in MCP-1 knockout and wild type mice, as was the expression of macrophage-derived cytokines, TNFα and IL-6, and levels of phosphorylated STAT3. The number of CCR2(+) cells in the liver was similar in MCP-1 knockout and wild type mice, which suggests that other chemokines may recruit CCR2(+) cells in the absence of MCP-1. Studies with CCR2 knockout mice revealed that hepatocyte proliferation was suppressed ~40 % compared to wild type mice 36 h after PH, but proliferation and liver-body-weight ratios were similar at 48 h.
Conclusion: These findings suggest that MCP-1 is not required for PH-induced liver regeneration, yet the role of CCR2 warrants further study.
Keywords: CCR2; Kupffer cells; Liver regeneration; MCP-1; Macrophages; Partial hepatectomy.