Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis

Microplastics (MPs), microparticles from plastic degradation, pose a substantial threat to human health. Macrophages, the body's immune sentinels, are unable to break down MPs, suggesting that MP accumulation could impair essential functions, such as removal of apoptotic cells (ACs), termed efferocytosis. We found that polystyrene MP (PS-MP) accumulation disrupted efferocytosis by impairing AC digestion in multiple types of macrophages and Sertoli cells, specialized testes phagocytes, in vitro. PS-MP exposure also suppressed efferocytosis and caused damage in the lungs, liver, and testes in vivo. Mechanistically, PS-MP-loaded efferocytotic macrophages had dysregulated metabolic and phagolysosome processes, including accumulation of methylglyoxal (MGO) and increased MGO glycation of glucose-6-phosphate dehydrogenase, an enzyme required for AC digestion. Consistently, we found that overexpression of the MGO detoxification glyoxalase-1 rescued PS-MP-induced defects in AC digestion in vitro and in vivo. Collectively, we demonstrate that PS-MPs directly disrupt efferocytosis, which negatively affects the function and health of multiple organs.