Dual route of polystyrene micro- and nanoplastics exposure increases in vivo leukocyte-endothelium interactions and aligns with organ injury.

Micro- and nanoplastics are pervasive environmental contaminants, yet direct in vivo evidence linking mixed-route exposure to leukocyte-endothelium interactions remains limited. Here, we investigated the effects of 28-day dual-route polystyrene exposure (oral microplastics and inhalational nanoplastics) in a sex-stratified murine model. Using intravital microscopy of mesenteric post-capillary venules, we quantified leukocyte rolling, stationary events and firm adhesion under physiological flow. Exposure increased leukocyte-endothelium interactions across the trafficking cascade compared with controls. Sex-stratified values are reported descriptively and are exploratory. Peripheral blood analysis showed higher total leukocyte counts and lymphocyte proportions in exposed animals. Fluorescence screening, restricted to the microplastic emission channel, revealed particle-associated signals on gastrointestinal tract, lung and brain surfaces. These organs exhibited biochemical and histopathological alterations, including increased lung malondialdehyde, reduced brain glutathione and structural injury in ileum, lung and brain tissues. Behavioral testing indicated impaired recognition and spatial working-memory-related performance, while anxiety-like behavior remained unaltered. These findings show that dual-route polystyrene exposure increases leukocyte-endothelium interactions in vivo, accompanied by organ-specific biochemical, structural and behavioral alterations. Because oral microplastics and inhaled nanoplastics were administered together and no single-route or single-size control group was included, the design does not allow the contribution of one route or one size class to be separated from the other. Endothelial activation, leukocyte activation, adhesion molecules and inflammatory mediators were not measured, so the increased interactions are reported here as an association and not as a demonstrated mechanism. This work supports leukocyte-endothelium interactions as a plausible physiological component contributing to the systemic response to micro- and nanoplastic exposure, highlighting the need for further studies of leukocyte and endothelial activation, inflammatory signaling and barrier dysfunction.