Related Experiment Video
Updated: Aug 15, 2026
Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
Tim4, a macrophage receptor for apoptotic cells, binds polystyrene microplastics via aromatic-aromatic interactions
Miki Kuroiwa1, Shin-Ichiro Yamaguchi1, Yoshinobu Kato1
1Laboratory of Immunology and Microbiology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Japan.
Abstract:
Understanding the interface between microplastics and biological systems will provide new insights into the impacts of microplastics on living organisms. When microplastics enter the body, they are engulfed preferentially by phagocytes such as macrophages. However, it is not fully understood how phagocytes recognize microplastics and how microplastics impact phagocyte functions. In this study, we demonstrate that T cell immunoglobulin mucin 4 (Tim4), a macrophage receptor for phosphatidylserine (PtdSer) on apoptotic cells, binds polystyrene (PS) microparticles as well as multi-walled carbon nanotubes (MWCNTs) through the extracellular aromatic cluster, revealing a novel interface between microplastics and biological systems via aromatic-aromatic interactions. Genetic deletion of Tim4 demonstrated that Tim4 is involved in macrophage engulfment of PS microplastics as well as of MWCNTs. While Tim4-mediated engulfment of MWCNTs causes NLRP3-dependent IL-1β secretion, that of PS microparticles does not. PS microparticles neither induce TNF-α, reactive oxygen species, nor nitric oxide production. These data indicate that PS microparticles are not inflammatory. The PtdSer-binding site of Tim4 contains an aromatic cluster that binds PS, and Tim4-mediated macrophage engulfment of apoptotic cells, a process called efferocytosis, was competitively blocked by PS microparticles. These data suggest that PS microplastics do not directly cause acute inflammation but perturb efferocytosis, raising concerns that chronic exposure to large amounts of PS microplastics may cause chronic inflammation leading to autoimmune diseases.
Insights
T cell immunoglobulin mucin 4 (Tim4) binds microplastics via aromatic interactions. While Tim4 mediates microplastic engulfment, polystyrene microplastics disrupt efferocytosis, potentially causing chronic inflammation and autoimmune diseases.
Area of Science:
- Immunology
- Materials Science
- Toxicology
Background:
- Microplastics are environmental contaminants with poorly understood biological interactions.
- Phagocytes, like macrophages, engulf microplastics, but recognition mechanisms and functional impacts remain unclear.
- T cell immunoglobulin mucin 4 (Tim4) is a macrophage receptor crucial for efferocytosis.
Purpose of the Study:
- To investigate the molecular mechanisms by which macrophages recognize microplastics.
- To determine the impact of microplastic-macrophage interactions on immune responses.
- To explore the potential of microplastics to interfere with efferocytosis.
Main Methods:
- Investigated binding of polystyrene (PS) microparticles and multi-walled carbon nanotubes (MWCNTs) to Tim4.
- Utilized genetic deletion of Tim4 in macrophages to assess its role in microplastic engulfment.
- Assessed inflammatory cytokine secretion (IL-1β, TNF-α) and reactive oxygen/nitric oxide production.
- Examined the effect of PS microparticles on Tim4-mediated efferocytosis of apoptotic cells.
Main Results:
- Tim4 binds PS microparticles and MWCNTs via its extracellular aromatic cluster, establishing a novel interaction interface.
- Tim4 mediates the engulfment of both PS microplastics and MWCNTs by macrophages.
- MWCNT engulfment triggers NLRP3-dependent IL-1β secretion, whereas PS microparticles do not induce acute inflammatory responses.
- PS microparticles competitively inhibit Tim4-mediated efferocytosis of apoptotic cells.
Conclusions:
- PS microplastics interact with macrophages through Tim4 but do not elicit acute inflammation.
- PS microplastics perturb efferocytosis, raising concerns for chronic inflammation and autoimmune disease development with prolonged exposure.
- Understanding microplastic-immune cell interfaces is critical for assessing their health risks.
