Polystyrene microplastics cross the murine intestine and induce inflammatory cell death after phagocytosis by human monocytes and neutrophils

Microplastics have been detected in human blood, raising concerns about human health. Here, we investigated the tissue distribution of microplastics after oral exposure in mice and their effects on mouse and human phagocytes. Both 1 and 10 μm polystyrene (PS) particles crossed the intestinal epithelium and were detected in the blood and liver of mice after ten days of oral administration. Intravital microscopy visualized <i>in vivo</i> phagocytosis of 1 μm PS by mouse neutrophils in the liver. Phagocytosis by human neutrophils required plasma or serum-coating of PS and was complement-dependent. Phagocytosis of coated PS induced monocyte and neutrophil cell death, with 10 μm PS requiring a single particle uptake, whereas 1 μm PS required much higher exposure levels. Neutrophil cell death upon 10 μm PS phagocytosis was characterized by extracellular DNA and classified as NETosis. These findings demonstrate that microplastics can penetrate tissues and provoke pro-inflammatory immune cell death, suggesting potential risks to human health.