Polystyrene microplastics-induced macrophage extracellular traps contributes to liver fibrotic injury by activating ROS/TGF-?/Smad2/3 signaling axis

Microplastics (MPs) are a type of emerging pollutant, posing a great threat to human and animal health. While recent studies have revealed the link between MPs exposure and liver injury of organisms, the effect of particle size on the level of MPs-induced hepatotoxicity and the intrinsic mechanism remain to be explored. Here, we established a mouse model exposed to two-diameter polystyrene MPs (PS-MPs, 1-10 mu m or 50-100 mu m) for 30 days. The in vivo results revealed that PS-MPs caused liver fibrotic injury in mice, accompanied with macro-phages recruitment and macrophage extracellular traps (METs) formation, which were negatively correlated with particle size. The data in vitro showed that PS-MPs treatment could induce macrophages to release METs in a reactive oxygen species (ROS)-independent manner, and the METs formation level caused by large-size par-ticles was higher than small-size particles. Further mechanistic analysis of a cell co-culture system revealed that PS-MPs-induced METs release led to a hepatocellular inflammatory response and epithelial-mesenchymal tran-sition (EMT) via activating the ROS/TGF-beta/Smad2/3 signaling axis, and this biological crosstalk could be relieved by DNase I. Overall, this findings demonstrates the key role of the action mechanism of METs in aggravating MPs-caused liver injury.