Neutrophil-Induced Liver Injury and Interactions Between Neutrophils and Liver Sinusoidal Endothelial Cells.

Abstract

Neutrophils are the most abundant type of leukocytes with diverse functions in immune defense including production of reactive oxygen species, bacteriocidal proteins, neutrophil extracellular traps, and pro-inflammatory mediators. However, aberrant accumulation of neutrophils in host tissues and excessive release of bacteriocidal compounds can lead to unexpected injury to host organs. Neutrophil-mediated liver injury has been reported in various types of liver diseases including liver ischemia/reperfusion injury, nonalcoholic fatty liver disease, endotoxin-induced liver injury, alcoholic liver disease, and drug-induced liver injury. Yet the mechanisms of neutrophil-induced hepatotoxicity in different liver diseases are complicated. Current knowledge of these mechanisms are summarized in this review. In addition, a substantial body of evidence has emerged showing that liver sinusoidal endothelial cells (LSECs) participate in several key steps of neutrophil-mediated liver injury including neutrophil recruitment, adhesion, transmigration, and activation. This review also highlights the current understanding of the interactions between LSECs and neutrophils in liver injury. The future challenge is to explore new targets for selectively interfering neutrophil-induced liver injury without impairing host defense function against microbial infection. Further understanding the role of LSECs in neutrophil-induced hepatotoxicity would aid in developing more selective therapeutic approaches for liver disease.