Activation of lands cycle-mediated inflammation in living macrophages exposed to label-free particulate matter

Abstract

Particulate matter (PM) is a pollutant of great concern and has severe impacts on human health. Macrophages (M phi) play a crucial role in the response to PM exposure, as they undergo metabolic reprogramming associated with inflammation. However, upon exposure to PM, the metabolic changes that occur in living M phi remain unclear. Here, we present evidence that PM activates Lands cycle-mediated inflammatory mechanisms using 3D-holotomography (3D-HT) technique integrated with multi-omics analysis. We show that internalization of PM results in abnormal lipid droplet (LD) dynamics, potentially leading to changes in lipid metabolite levels. Additionally, our multi-omics data reveal that alterations in lipid metabolism mediated by the Lands cycle leads to the increased production of inflammatory lipid mediators, including lysophospholipids, ceramides and sphingomyelins. Furthermore, by performing lipid metabolic imaging in living M phi, we elucidated changes in the activity of altered lipid metabolism and the spatiotemporal correlation between inflammation and LD dynamics. Our findings suggest that the developed approach can provide a new experimental strategy to identify lipid metabolism biomarkers in living cells upon PM exposure.