Justin Perry, Associate Member at Memorial Sloan Kettering Cancer Center, shared a post on LinkedIn:
“Those who know me, know I’m not someone who changes his preferences & behaviors lightly. As Ron Swanson said, ‘I regret nothing. The end.’ Well, let me tell you about our new study, out from our lab at Memorial Sloan Kettering Cancer Center in Immunity by Cell Press which is the exception.
This is the first paper from our lab under the new The National Institutes of Health/ U.S. Department of Health and Human Services (HHS) guidelines for open access.
Plastics are a ubiquitous part of everyday life, but growing evidence suggests that the microparticles from plastic degradation, microplastics (MPs), pose a significant threat to human health.
These MPs, commonly ingested or inhaled via environmental exposure, first encounter professional phagocytes, such as macrophages (the body’s ‘big eaters’), that live in all tissues of the body and perform essential tasks.
One of these essential tasks, the phagocytosis of dead cells (we call it ‘efferocytosis’), is the process by which our phagocytes literally engulf your body’s dead cells, something that happens >3 million times per second! You can see why this matters.
Previous studies have shown that your body’s macrophages can eat MPs. However, if & how these MPs affect efferocytosis is unknown.
Here, we report the alarming finding that exposure to MPs significantly impairs efferocytosis in multiple mice tissues and by human macrophages (Figure 1). Specifically, we found that both mouse and human macrophages exposed to MPs internalize fewer dead cells & have significantly delayed digestion of engulfed dead cells in vitro.
Using multiple mouse models (Figure 2), we found MP exposure disrupts efferocytosis in the lung, liver, and testis in vivo, negatively affecting each tissue. In the case of the testes, this caused decreased fertility in male mice.
Scarily, these effects were not limited to efferocytosis, as MPs also suppressed bacterial, fungal, and antibody-mediated phagocytosis in vitro and the phagocytic uptake and killing of A. fumigatus (a fungal infection model) in the lungs of mice in vivo (Figure 3).
We sought to learn how MPs are causing these defects (Figure 4 and 5). The results were striking: The presence of MPs in macrophages engulfing dead cells accumulated the metabolite methylglyoxal (MGO). MGO forms Advanced Glycation End Products, associated w/ many chronic diseases.
Strikingly, we found increased ‘MGOylation‘ (MGO binding) of proteins, including the enzyme G6PD. G6PD is required for efficient degradation of engulfed dead cells.
We next had the crazy idea that, maybe, we could give macrophages the ability to combat MGO accumulation by a process my colleague Kayvan R. Keshari coined ‘metabolic engineering’. It turns out, there is an enzyme (called Glo1) that detoxifies MGO. Excitingly, engineering macrophages w/ Glo1 significantly rescued MP-mediated efferocytosis impairments both in vitro and in vivo! (Figure 6).”
Title: Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis
Authors: Ana C. Codo, Jesus E. Romero-Pichardo, Zhaoquan Wang, Mariano A. Aufiero, Tomi Lazarov, Waleska Saitz Rojas, Nicole S. Walker, Achuth Nair, Roger F. Cole, Savannah Adkins, Edward Dong, Kelvin Fadojutimi, Celia Martínez de la Torre, Yael David, Tobias M. Hohl, Frederic Geissmann, Kayvan R. Keshari, Christopher D. Lucas, Justin S.A. Perry
Read The Full Article
Other articles featuring Justin Perry on OncoDaily.