Scientists have shed light on how macrophages interact with microplastics

A large portion of the approximately 200 million tons of single-use plastic produced globally is disposed as waste. The eventual breakdown of this plastic into microplastics – particles 0.1-1000 micrometers in size – is a cause for concern. Humans are exposed to microplastics not only through food consumption but also through inhalation, and their occurrence in the bloodstream and organs has already been documented.

It is not known whether chronic exposure to microplastics affects human health, but they are targeted by phagocytosis—the process of swallowing foreign particles—by macrophages. Irrespective of pathogens, macrophages recognize environmental particles such as nanomaterials by recognizing patterns in specific parts of specific targets of phagocytosis. Although considered biological and non-inflammatory, it is not known how microplastics are recognized by macrophages and how their function is affected after microplastic ingestion.

Now, a group of researchers at Ritsumeikan University and Shimane University has shed light on how polystyrene (PS) microplastics interact with macrophages. Their findings have been published in the journal macroenvironmental science.

The research team, led by Professor Masafumi Nakayama of Ritsumeikan University, discovered the role of the previously unknown aromatic-aromatic interface between PS microplastics and the T-cell immunoglobulin receptor (Tim4) on macrophages. Their previous research revealed that Tim4 recognizes carbon nanotubes (particles that cannot be digested after phagocytosis but trigger inflammation).

“We were keen to find out if Tim4 binds to PS which consists of aromatic styrene units, and if this interaction perturbs the immune response,” says Professor Nakayama when asked about his motivation for the study.

The group took advantage of molecular techniques and human and mouse cell lines to study PS microplastic recognition. They measured apoptosis (the engulfment of apoptotic cells by macrophages) and monitored the immune response by determining reactive oxygen species (ROS), nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF) -α) production after exposure to PS.

The group found that macrophages generated as Tim4 deletion mutants were unable to ingest PS microplastics or multi-walled carbon nanotubes (MWCNTs), confirming a role for Tim4 in PS recognition.

Explaining the main findings, Professor Nakayama says, “While MWCNT ingestion did produce an immune response, the PS microplastics used in this study did not stimulate the release of NO, ROS, or TNF-α. This indicates that the PS microplastics are not inflamed. And that macrophages can distinguish between particles, too.”

The results revealed that the binding site on Tim4 contains an aromatic group on an extracellular loop bound to PS, and furthermore, that PS microplastics competitively inhibit the process of cell proliferation. This is important because it highlights that PS microplastics do not directly promote acute inflammation; However, exposure to large amounts of PS microplastics may cause chronic inflammation, leading to autoimmune diseases.

The group is excited about their discovery of the new interface between microplastics and the biological system. Regarding future avenues of research, Prof. Nakayama concludes: “We have laid the foundation for providing a better understanding of the absorption, distribution, excretion, and toxicity of bioavailable microplastics.”