Neutrophil extracellular traps mediate pathophysiology of hepatic cells during liver injury

Abstract Neutrophil extracellular traps (NETs) are web‐like, bactericidal structures produced by neutrophils and are composed principally of extracellular DNA, histones, elastase, and myeloperoxidase, among other components. NET formation is an innate immune response that is beneficial for pathogen killing and clearance. However, excessive NET formation and clearance defects can lead to inflammation and induce damage to host organs. NETs are also implicated in the development of noninfectious inflammatory disorders, such as liver injury in chronic liver diseases. The liver parenchyma contains hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells. Each of these cells possesses unique structures and functions, and their interactions with NETs result in pathophysiological changes contributing to liver injury. This review updates the findings related to the modes of action and molecular mechanisms by which NETs modulate the pathophysiology of various hepatic cells and potentiate liver injury. The article also reviews the roles of NETs in hepatic ischemia reperfusion injury, hepatocellular carcinoma pathogenesis, and cancer metastasis. Last, we examine data to determine whether NETs induce crosstalk among various hepatic cells during liver injury and to identify future research directions.