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Origin matters – investigating the immunomodulatory effects of primary and secondary micro- and nanoplastics on human macrophages.
Summary
This study compared immune responses triggered by primary microplastics versus secondary microplastics derived from environmental weathering, using macrophage models. Secondary microplastics, which are more environmentally realistic, produced distinct immunomodulatory effects compared to primary particles.
Micro- and nanoplastic particles (MNP) are recognized as pervasive environmental contaminants, prompting concerns over their potential health impacts. Research has concentrated mainly on primary MNP, with limited attention to the more abundant secondary MNP derived from plastic fragmentation. Macrophages play a critical role in MNP uptake and response but specific interactions between MNP properties and macrophage behaviour, particularly with secondary MNP, remain poorly understood. This study investigates the cytotoxic and immunomodulatory effects of primary and secondary MNP on human THP-1 macrophages after up to 24 hours of exposure to 1, 10 and 100 µg/ml. We assessed the impact of mechanically degraded secondary polyvinyl chloride, polypropylene, and polyamide particles (PVC, PP; Results show concentration-, time-, and size-dependent uptake of primary PS. Secondary MNP induce lysosomal activity, indicating intralysosomal accumulation. Dose-dependent cytotoxic effects are found, characterized by reduced mitochondrial activity and increased lactate dehydrogenase leakage. Interestingly, secondary MNP fail to stimulate cytokine production (IL-6, TNF-α, IL-1β) and NF-κB activity in macrophages. Our study unveils the effects of secondary PVC, PP, and PA 6.6, contributing to a better understanding of the potential risks associated with human exposure to MNP. Macrophages do not exhibit a direct pro-inflammatory response at sub-cytotoxic concentrations of MNP. However, higher concentrations of secondary MNP induce cytotoxicity, potentially impacting immune function indirectly. Our findings highlight the importance of studying secondary PS in MNP-related health risks research. Future research should prioritize examining secondary and environmentally relevant MNP produced through milling and weathering processes to understand their altered properties and potential health effects. This study is supported by the EC Horizon 2020-project POLYRISK [Grant ID 964766] and the ZonMw/Health Holland project MOMENTUM [Grant ID 458001101]. Also see: https://micro2024.sciencesconf.org/559336/document
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