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Microplastics induced apoptosis in macrophages by promoting ROS generation and altering metabolic profiles
Lijuan Wang1, Wenlong Pei2, Jiacong Li3
1Department of Pathogen Biology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, PR China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, PR China.
Abstract:
The ubiquitous presence of Microplastics (MPs) in various environments documented in recent years has recently raised significant concerns about their toxic effects. While macrophages serve as the first line of defense against toxic substances and pathogens, the impact and mechanisms of microplastics on these immune cells remain unclear. This study aims to explore whether MPs induce macrophage apoptosis through the promotion of reactive oxygen species (ROS) generation and alterations in metabolic profiles. The viability of RAW264.7 cells decreased as the concentration of 0.5 µm or 5 µm MPs ranged from 0.2 to 1.5 mg/mL, with a more pronounced effect observed in the 0.5 µm MPs group. Zebrafish exposed to 0.5 µm or 5 µm MPs at a concentration of 0.5 mg/mL exhibited decreased macrophage abundance and increased apoptosis, accompanied by alterations in the expression of inflammatory and apoptosis-related genes. While 0.5 µm MPs were observed to enter macrophages, 5 µm MPs only adhered to the cell membrane surface. Both particle sizes induced ROS generation and disrupted cellular metabolism in RAW264.7 cells. Notably, macrophages exhibited a more pronounced response to 0.5 µm MPs, characterized by heightened ROS generation, increased secretion of pro-inflammatory mediators, and a significant decrease in sphingolipid metabolism. These findings suggest that the adverse effects on macrophages are greater with 0.5 µm MPs compared to 5 µm MPs, possibly attributed to particle size effects. This study contributes additional evidence on the impact of MPs on human immune cells.
Insights
Microplastics (MPs) harm immune cells. Smaller MPs (0.5 µm) induce more macrophage apoptosis and metabolic disruption than larger ones (5 µm), highlighting particle size as a key factor in microplastic toxicity.
Area of Science:
- Environmental Science
- Immunotoxicology
- Cell Biology
Background:
- Microplastics (MPs) are pervasive environmental contaminants with growing concerns regarding their toxicological effects.
- Macrophages are critical immune cells, but the impact of MPs on their function and survival is not fully understood.
Purpose of the Study:
- To investigate the effects of different microplastic sizes on macrophage apoptosis.
- To elucidate the mechanisms involving reactive oxygen species (ROS) generation and metabolic alterations.
Main Methods:
- Exposure of RAW264.7 cells and zebrafish to 0.5 µm and 5 µm MPs.
- Assessment of cell viability, macrophage abundance, apoptosis, gene expression, ROS production, and metabolic profiles.
Main Results:
- Both MP sizes reduced RAW264.7 cell viability and induced apoptosis in zebrafish macrophages.
- 0.5 µm MPs caused more pronounced ROS generation, pro-inflammatory mediator secretion, and sphingolipid metabolism disruption.
- Smaller MPs (0.5 µm) were internalized by macrophages, while larger MPs (5 µm) adhered to the surface.
Conclusions:
- Microplastic exposure induces macrophage apoptosis and metabolic dysfunction.
- Smaller microplastics (0.5 µm) exhibit greater toxicity to macrophages compared to larger ones (5 µm).
- Particle size is a critical determinant of microplastic immunotoxicity.

