Repeated exposure to polyethylene microplastic mixtures containing PFAS and bisphenols activates THP-1 macrophages
Lucas Gaillard1, Léo Sportes-Milot1, Kloé Debizet1
1INSERM, Health & Functional Exposomics - HealthFex Unit, Université Paris Cité, Paris, France.
Abstract:
Microplastics (MPs) are pervasive in the environment and are toxic due to the nature of their polymers and associated additives, such as bisphenols (BPs) and per- and polyfluoroalkyl substances (PFAS). Nonetheless, there is a scarcity of in vitro studies investigating the toxicity of MPs combined with these additives and deciphering the underlying mechanisms in the context of recurrent exposures, which more accurately reflect human contamination. The objective of this study is to assess the differential toxic impacts of polyethylene microplastics (PE-MPs, 100 μg/mL) and a mixture of additives (i.e., AddMix containing 10 μM of BPA, BPS, PFOS, and PFOA) on naive THP-1 macrophages during unique or three repeated exposures over five days. Scanning electron and Raman microscopy images indicated an effective internalization of PE-MPs by macrophages after 30 min and 24 h of exposure. Three repeated exposures of THP-1 macrophages to PE-MPs and PE-MPs + AddMix over five days increased mitochondrial ROS production by 19 % and 13 %, respectively, and led to a more pronounced glycolytic phenotype, associated with the enhanced secretion of the pro-inflammatory cytokine IL-1β by 38 % with PE-MPs. Analysis of transcriptomic data revealed that PE-MPs and/or AddMix significantly enhanced the expression of genes primarily related to inflammation and modulation of lipid metabolism pathways. Our work highlights that MPs mixtures with additives, particularly upon repeated exposure, are recognized by macrophages as activation signals, leading to stimulation of inflammatory pathways, which require further investigation to be fully deciphered.
Insights
Repeated exposure to microplastics (MPs) and chemical additives triggers inflammatory responses in immune cells. This study reveals MPs mixtures activate macrophages, increasing pro-inflammatory cytokine release and altering cellular metabolism, highlighting risks of environmental contaminants.
Area of Science:
- Environmental Toxicology
- Cellular Biology
- Immunology
Background:
- Microplastics (MPs) are prevalent environmental pollutants, posing toxicity risks due to their polymeric nature and associated chemical additives like bisphenols (BPs) and per- and polyfluoroalkyl substances (PFAS).
- Limited in vitro research exists on the combined toxicity of MPs and additives, especially concerning mechanisms of recurrent exposure mimicking human contamination.
Purpose of the Study:
- To evaluate the distinct toxic effects of polyethylene microplastics (PE-MPs) and a mixture of additives (BPA, BPS, PFOS, PFOA) on THP-1 macrophages.
- To investigate the impacts of both single and repeated exposures (over five days) on macrophage responses and underlying molecular mechanisms.
Main Methods:
- THP-1 macrophages were exposed to PE-MPs (100 μg/mL) and an additive mixture (AddMix, 10 μM each of BPA, BPS, PFOS, PFOA) under single and repeated exposure conditions.
- Internalization of PE-MPs was confirmed using scanning electron and Raman microscopy.
- Cellular responses including mitochondrial ROS production, glycolytic phenotype, IL-1β secretion, and gene expression (transcriptomics) were analyzed.
Main Results:
- PE-MPs were effectively internalized by macrophages.
- Repeated exposure to PE-MPs and PE-MPs+AddMix significantly increased mitochondrial ROS production (19% and 13%, respectively) and promoted a glycolytic phenotype.
- PE-MPs exposure led to a significant increase in IL-1β secretion (38%), and transcriptomic analysis revealed enhanced expression of inflammation- and lipid metabolism-related genes.
Conclusions:
- Microplastic-additive mixtures, particularly upon repeated exposure, are recognized by macrophages as potent activators.
- These exposures stimulate inflammatory pathways and alter cellular metabolism, underscoring the potential health risks associated with complex environmental contaminant mixtures.
- Further research is needed to fully elucidate the mechanisms behind these observed inflammatory responses.
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