Activation of lands cycle-mediated inflammation in living macrophages exposed to label-free particulate matter
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Published on: July 12, 2024
Jeongwon Park1, Jueun Lee2, Hyun-Jin Kim3
1Aging Research Group, Honam Regional Center, Korea Basic Science Institute, Gwangju 61751, South Korea; Department of Animal Science, Chonnam National University, Gwangju 61186, South Korea.
Abstract:
Particulate matter (PM) is a pollutant of great concern and has severe impacts on human health. Macrophages (Mφ) 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 Mφ 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 Mφ, 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.
Insights
Particulate matter exposure triggers inflammatory responses in macrophages by altering lipid metabolism via the Lands cycle. This study reveals dynamic changes in lipid droplets and inflammatory mediators in living cells.
Area of Science:
- Environmental Health
- Cell Biology
- Metabolomics
Background:
- Particulate matter (PM) is a significant environmental pollutant impacting human health.
- Macrophages (Mφ) are key immune cells involved in PM response, undergoing metabolic reprogramming linked to inflammation.
- Metabolic changes in living Mφ upon PM exposure are not fully understood.
Purpose of the Study:
- To investigate the metabolic alterations in living macrophages following particulate matter exposure.
- To elucidate the role of the Lands cycle in PM-induced inflammation.
- To establish a novel imaging strategy for studying cellular responses to PM.
Main Methods:
- Utilized 3D-holotomography (3D-HT) integrated with multi-omics analysis.
- Performed lipid metabolic imaging in living macrophages.
- Analyzed lipid droplet dynamics and inflammatory mediator production.
Main Results:
- PM exposure activates Lands cycle-mediated inflammatory mechanisms in macrophages.
- Internalization of PM leads to abnormal lipid droplet dynamics and altered lipid metabolite levels.
- Increased production of inflammatory lipid mediators (lysophospholipids, ceramides, sphingomyelins) was observed.
- Elucidated spatiotemporal correlation between inflammation and lipid droplet dynamics in living Mφ.
Conclusions:
- PM exposure induces significant metabolic reprogramming in macrophages, involving the Lands cycle and lipid metabolism.
- The developed 3D-HT and multi-omics approach provides a new strategy to identify lipid metabolism biomarkers in living cells exposed to pollutants.
- Understanding these cellular mechanisms is crucial for assessing the health impacts of particulate matter.
