Fig. 3

CXCR2 regulates neutrophils in the inflamed liver at acute and post-acute phases of sepsis. For the acute phase of sepsis, mature circulating neutrophils with high expression of CXCR2 activate and migrate from the blood flow to the liver via chemoattractant CXCLs, especially for IL-8 released from LSECs, KuCs, HSCs, and hepatocytes. Activated neutrophils display a wide range of effector mechanisms to counteract pathogens, which include the secretion of pro-inflammation mediators, ROS, phagocytosis, and NETs while damaging liver parenchymal cells as well. However, in the post-acute phase of sepsis, the endothelial barrier damage leads to immature neutrophils with lower expression of CXCR2 trafficking to the liver, with dysfunction of neutrophils, including migration, secretion of inflammatory mediators, and secretion and phagocytosis for pathogens. In addition, impaired neutrophils have suppressive immunity for other immune cells and excessive injury for the hepatocytes via ROS and NETs, which drive liver failure in sepsis. ROS, reactive oxygen species; NETs, neutrophils extracellular traps