The Contribution of Hepatic Macrophage Heterogeneity during Liver Regeneration after Partial Hepatectomy in Mice

METHODS: In the present study, we investigated hepatic macrophage heterogeneity in murine liver regeneration after 2/3 PHx through immunofluorescence staining, fluorescence-activated cell sorting analysis, and quantitative reverse transcription-polymerase chain reaction. RESULTS: Our research showed that Kupffer cells reduced rapidly in the early PHx and restored gradually depending on local proliferation and replenishment from infiltrating monocyte-derived macrophages. The ratio of ly6C(hi) to ly6C(lo) subset of macrophages in the liver changed dynamically, and hepatic macrophage function exhibits a significant difference in different stages of liver regeneration. Moreover, blocking infiltrating monocyte-derived macrophage recruitment augmented Kupffer cell proliferation but impaired the restoration of the hepatic macrophage pool, which led to delayed hepatocyte mitosis and liver regeneration. CONCLUSIONS: Our data suggest that hepatic macrophage changes dynamically in origin and function during liver regeneration following PHx and macrophage-targeted liver regeneration should consider macrophage heterogeneity.