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Updated: Feb 28, 2026
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Published on: July 27, 2022
Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis
Ana C Codo1, Jesus E Romero-Pichardo2, Zhaoquan Wang1
1Immunology & Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Microplastics (MPs), microparticles from plastic degradation, pose a substantial threat to human health. Macrophages, the body's immune sentinels, are unable to break down MPs, suggesting that MP accumulation could impair essential functions, such as removal of apoptotic cells (ACs), termed efferocytosis. We found that polystyrene MP (PS-MP) accumulation disrupted efferocytosis by impairing AC digestion in multiple types of macrophages and Sertoli cells, specialized testes phagocytes, in vitro. PS-MP exposure also suppressed efferocytosis and caused damage in the lungs, liver, and testes in vivo. Mechanistically, PS-MP-loaded efferocytotic macrophages had dysregulated metabolic and phagolysosome processes, including accumulation of methylglyoxal (MGO) and increased MGO glycation of glucose-6-phosphate dehydrogenase, an enzyme required for AC digestion. Consistently, we found that overexpression of the MGO detoxification glyoxalase-1 rescued PS-MP-induced defects in AC digestion in vitro and in vivo. Collectively, we demonstrate that PS-MPs directly disrupt efferocytosis, which negatively affects the function and health of multiple organs.
Insights
Microplastics (MPs) impair the immune system's ability to clear dead cells, a process called efferocytosis. This disruption leads to organ damage and impaired cellular functions due to metabolic changes.
Area of Science:
- Environmental Health
- Immunology
- Toxicology
Background:
- Microplastics (MPs) are pervasive pollutants with potential human health risks.
- Macrophages are crucial immune cells for clearing cellular debris, a process known as efferocytosis.
- MP accumulation may compromise efferocytosis, leading to impaired immune function and organ damage.
Purpose of the Study:
- To investigate the impact of polystyrene microplastics (PS-MPs) on efferocytosis.
- To elucidate the mechanisms by which PS-MPs disrupt efferocytosis.
- To assess the in vivo effects of PS-MPs on organ health and efferocytosis.
Main Methods:
- In vitro studies using macrophages and Sertoli cells exposed to PS-MPs.
- In vivo studies assessing PS-MP effects on lungs, liver, and testes.
- Analysis of metabolic and phagolysosome processes in MP-exposed cells.
- Investigating the role of methylglyoxal (MGO) and glyoxalase-1.
Main Results:
- PS-MP accumulation disrupted efferocytosis by impairing apoptotic cell digestion in macrophages and Sertoli cells.
- In vivo, PS-MP exposure suppressed efferocytosis and caused organ damage in lungs, liver, and testes.
- Mechanistically, PS-MPs led to methylglyoxal accumulation and impaired glucose-6-phosphate dehydrogenase, hindering efferocytosis.
Conclusions:
- PS-MPs directly disrupt efferocytosis, impacting cellular functions and organ health.
- Methylglyoxal accumulation is a key mechanism in PS-MP-induced efferocytosis defects.
- Overexpression of glyoxalase-1 can mitigate PS-MP-induced efferocytosis impairment.
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