Neutrophil-Nanoplastic Interaction via Mac-1 (CD11b/CD18) Drives Neutrophil Dysfunction

Nanoplastics (NPs) are increasingly prevalent in modern environments, raising significant concerns about their potential impact on human health. Given their small size and diverse surface chemistries, NPs can trigger immune responses in a pathogen-like manner. Although neutrophils interact with non-biological foreign particles, the molecular mechanisms remain poorly understood. In this study, we demonstrate that polystyrene-NPs exhibit cytotoxic effects on neutrophils, leading to cell death. NPs-treated neutrophils showed increased production of ROS, enhanced secretion of pro-inflammatory cytokines, and reduced release of anti-inflammatory cytokines. Mechanistically, NP exposure increased surface levels of Mac-1 on neutrophils. Inhibition of this integrin suppressed neutrophil-NP interaction, reducing production of ROS and pro-inflammatory cytokines, and diminished neutrophil infiltration into the lungs of NPs-exposed mice. Overall, our findings provide new insights into how NPs engage innate immune cells and suggest that targeting Mac-1 may represent a promising therapeutic strategy for mitigating NP-induced inflammation.