Polystyrene Microplastics Induce Inflammatory Responses and Promote M2‐Associated Cytokine Expression in Mouse Lung Tissues

ABSTRACT Microplastic pollution, particularly polystyrene microplastics (PS‐MPs), poses significant environmental and health risks; however, its biological effects remain poorly understood. PS‐MPs are persistent in the environment and can accumulate in biological tissues, raising concerns regarding their potential health effects. Although previous studies highlight oxidative stress and inflammation from microplastics, the specific immune responses in lung tissues remain underexplored. Therefore, the present study was conducted to investigate the biodistribution of PS‐MPs and the inflammatory response induced by them in lung tissues. Fragmented PS‐MPs (10–50 μm, 2000 mg/kg oral exposure) were manufactured and subjected to physical and chemical characterization using particle size analyzers, Raman spectroscopy, and scanning electron microscopy. Fluorescence imaging was performed using cyanine 5.5 carboxylic acid‐labeled PS‐MPs (Cy‐PS‐MPs) for tracking particle distribution. Ex vivo imaging confirmed the accumulation of Cy‐PS‐MPs in lung tissues, which was further validated by Raman spectroscopy. Histopathological analyses revealed granulomatous inflammation with macrophage infiltration in treated groups, along with significant upregulation of TGF‐β and IL‐10, cytokines commonly associated with M2 macrophage responses. These results emphasize the immunomodulatory and inflammatory responses induced by PS‐MPs, providing insights into their mechanisms of action and potential health effects. Therefore, this study suggests the importance of understanding chronic immune responses and tissue remodeling following exposure to microplastics, which could contribute to long‐term respiratory pathologies and fibrosis.