Polystyrene microplastics promote liver inflammation by inducing the formation of macrophages extracellular traps.

Microplastics (MPs), a new and increasing environmental pollutant, can cause ongoing damage to organisms. Although recent studies have revealed mechanisms of action for some of the hepatotoxicity caused by MPs, the role-played by cellular interactions, particularly immune cells, in the process of liver injury has not been elucidated. In the present study, 5-μm polystyrene microplastics (PS-MPs) induced liver inflammation as well as the formation of Macrophage extracellular traps (METs). Macrophage and LMH cell co-culture systems confirmed that PS-MPs-induced METs promote inflammation in hepatocytes. Mechanistically, macrophages actively phagocytose particles after 4 h of exposure to PS-MPs. Subsequently PS-MPs elevated ROS levels and disrupt mitochondrial kinetic homeostasis. Further activation of mitochondrial autophagy and lysosomes. After phagocytosis of PS-MPs by macrophages for 12 h, continued autophagy and lysosome activation eventually lead to lysosome rupture and release of calcium ions to induce the formation of METs. Blocking ROS (NAC) and autophagy (3MA) partially alleviated mitochondrial and lysosomal damage and thus inhibited the formation of METs induced by PS-MPs. NAC also delayed the onset of respiratory burst to alleviate METs formation. In conclusion, our study reveals the mechanism of METs formation in liver inflammation induced by PS-MPs exposure and suggests that lysosomal damage may be one of the key players in the formation of METs induced by PS-MPs.