BACKGROUND In the context of hepatobiliary and liver transplant surgery,ischemia-reperfusion(I/R)injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammator...BACKGROUND In the context of hepatobiliary and liver transplant surgery,ischemia-reperfusion(I/R)injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammatory response to reperfusion.Ma-crophages can drive inflammation in response to injury,but they can also pro-mote liver growth and resolution of chronic liver injury and fibrosis.In chronic liver injury models in mice,macrophage colony stimulating factor(CSF)1 stimu-lates pro-regenerative macrophages.AIM To determine whether stimulation of macrophages with macrophage CSF could promote liver repair after I/R injury.METHODS We investigated the impact of perisurgical treatment with a long-circulating CSF1-Fc conjugate on liver injury and hepatocyte proliferation after 70%ischemia for 60 minutes at 6 hours,48 hours and 7 days post reperfusion in rats.Circulating and liver tissue monocyte and macrophage subsets in the ischaemic and oxyge-nated lobes were assessed using quantitative PCR and flow cytometry.RESULTS CSF1-Fc treatment did not affect the extent of hepatocellular injury post-reperfu-sion,as indicated by serum transaminases.Liver I/R injury,especially necrotic area,was reduced in CSF1-Fc-treated rats 48 h post-surgery.This was associated with increased accumulation of macrophages in both the oxygenated and ischemic lobes(ILs),and peri-necrotic zone localization in the IL.CSF1-Fc treatment also promoted liver growth,associated with increased parenchymal and non-parenchymal cell proliferation.CSF1-Fc increased the abundance of CD43+non-classical monocytes,consistent with the role of CSF1 signaling in monocyte maturation,and increased CD163 expression on mature macrophages.CONCLUSION This study suggests CSF1 stimulation drives monocytes/macrophages towards a pro-regenerative response and perisurgical CSF1 treatment might augment liver regeneration in patients undergoing liver resection.展开更多
基金Supported by the German Research Foundation(Deutsche Forschungsgemeinschaft)and the Australian National Health and Medical Research Council and the Mater Foundation.
文摘BACKGROUND In the context of hepatobiliary and liver transplant surgery,ischemia-reperfusion(I/R)injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammatory response to reperfusion.Ma-crophages can drive inflammation in response to injury,but they can also pro-mote liver growth and resolution of chronic liver injury and fibrosis.In chronic liver injury models in mice,macrophage colony stimulating factor(CSF)1 stimu-lates pro-regenerative macrophages.AIM To determine whether stimulation of macrophages with macrophage CSF could promote liver repair after I/R injury.METHODS We investigated the impact of perisurgical treatment with a long-circulating CSF1-Fc conjugate on liver injury and hepatocyte proliferation after 70%ischemia for 60 minutes at 6 hours,48 hours and 7 days post reperfusion in rats.Circulating and liver tissue monocyte and macrophage subsets in the ischaemic and oxyge-nated lobes were assessed using quantitative PCR and flow cytometry.RESULTS CSF1-Fc treatment did not affect the extent of hepatocellular injury post-reperfu-sion,as indicated by serum transaminases.Liver I/R injury,especially necrotic area,was reduced in CSF1-Fc-treated rats 48 h post-surgery.This was associated with increased accumulation of macrophages in both the oxygenated and ischemic lobes(ILs),and peri-necrotic zone localization in the IL.CSF1-Fc treatment also promoted liver growth,associated with increased parenchymal and non-parenchymal cell proliferation.CSF1-Fc increased the abundance of CD43+non-classical monocytes,consistent with the role of CSF1 signaling in monocyte maturation,and increased CD163 expression on mature macrophages.CONCLUSION This study suggests CSF1 stimulation drives monocytes/macrophages towards a pro-regenerative response and perisurgical CSF1 treatment might augment liver regeneration in patients undergoing liver resection.
