For the first time in the world, researchers have confirmed in real-time imaging with quantitative analysis the process by which fine dust disrupts lipid metabolism inside immune cells (the process of making and using fats within cells) and sustains inflammation. Although related mechanisms have been proposed in academia, this is the first case to prove in one sequence how fine dust accumulates inside cells, lipid metabolism changes, and inflammation is activated.
Research teams led by Lee Seong-su and Hwang Geum-suk at the Korea Basic Science Institute (KBSI) and by Kim Seong-hak at Chonnam National University said on the 4th that fine dust reprograms the lipid metabolism of macrophages (immune cells that engulf foreign substances in the body), hyperactivates the Lands cycle, and that this process persistently induces inflammation. The Lands cycle is the process of reorganizing membrane components (phospholipids), and when excessively activated, it produces many pro-inflammatory substances that sustain inflammation.
In the research community, it has been partly reported that fine dust stimulates macrophages to cause inflammation and that lipid metabolism is involved. However, no study had shown which step occurs first, which enzymes drive it, and how it proceeds in real time in living cells.
After treating mouse macrophages with standard fine dust, the team observed intracellular changes using three-dimensional holotomography (3D-HT, an imaging technology that observes internal structures in 3D without damaging cells). As a result, they confirmed that fine dust taken into the cell accumulates and that lipid droplets (lipid droplets, small droplets formed by aggregated lipid components within cells) increase. This is the first visual confirmation that fine dust disrupts cellular structure and metabolic balance.
In real-time quantitative analysis, the inflammatory response switched on first, followed by repeated observations of lipid droplet accumulation. Therefore, changes in lipid metabolism were confirmed to be not just a byproduct but a core process that amplifies and sustains inflammation.
Conventional 3D-HT was useful for observing cell morphology and the influx of fine particles, but it had limits in quantitatively capturing changes in cell metabolism. To address this, the researchers developed a multimodal analytical method that combines 3D-HT with multiomics (a technology that analyzes multiple biological information simultaneously), particularly lipidomics (analysis of lipid components in cells) and transcriptomics (a technology that analyzes changes in gene expression).
Through this, they identified a total of 234 lipid species and found that lipid metabolites such as arachidonic acid, which generate inflammatory signals, increased by 2 to 3 times. Transcriptomic analysis also showed up to a 4 to 6 times increase in the expression of PLA2 enzymes and genes related to the Lands cycle, along with increases in inflammatory genes (Tnf, Ccl2, Ptgs2, etc.).
As a result, fine dust excessively drove the PLA2–Lands cycle pathway, overproducing the inflammatory mediator PGE2 (a substance that transmits inflammatory signals). In fact, inhibiting PLA2 reduced PGE2 by 40 to 50%. In other words, the PLA2–Lands cycle was functionally confirmed to be the key pathway of fine dust–induced inflammation.
KBSI researcher Lee Seong-su said, "This is the first case to confirm in real time and quantitatively how an inflammatory pathway operates in living cells," and noted, "It will be used in toxicity assessments of harmful environmental particles and research on inflammatory diseases." KBSI researcher Hwang Geum-suk said, "We have precisely identified the process by which fine dust disrupts cellular lipid metabolism to induce inflammation," and added, "We will continue research on harmful environmental factors such as fine dust, microplastics and heavy metals."
The findings were published on Oct. 5 in the Journal of Hazardous Materials.