Abstract
Macrophage lipid metabolism plays a pivotal role in innate and adaptive immune responses. Previous studies have shown that this process plays a role in infections and contributes to the pathogenesis of diabetes, atherosclerosis, and other immunometabolic diseases. M1 macrophages, or classically activated macrophages, are key players in the defense against bacterial infections. M2 macrophages, or alternatively activated macrophages, are involved in anti-inflammatory responses. Using the multiple reaction monitoring method, we identified changes in lipid composition during the differentiation of human and murine macrophages. We detected over 300 lipid molecules in mammalian macrophages, and we observed a striking shift in the composition of glycerophospholipids (GLs) from saturated and monounsaturated to polyunsaturated during human macrophage polarization. Moreover, M2 macrophages showed a higher level of lysophospholipids (lysoGLs) than did M1 macrophages. The lysoPI species increased in human and mouse M2 macrophages, suggesting that they may be involved in M2 macrophage polarization and anti-inflammatory processes. Collectively, these results indicate that lipids may play a role in the pro- and anti-inflammatory activities of macrophages and may be markers of the macrophage activation state.
Highlights
Macrophages, nonspecific components of the innate immune system, are present in all tissues of the body
We identified more than 300 lipid molecules in mammalian macrophages using liquid chromatography-mass spectrometry (LC-MS) with multiple reaction monitoring (MRM) scanning, which simultaneously detects a broad spectrum of lipid molecules
M2 cells showed the opposite tendency, with a decrease in PC, PE, and PI species and an increase in PG species (Supplementary Fig. 2d). These results indicated that the lipidomics profiles of THP-1 cells and human primary monocyte-derived macrophages were consistent, each has some level of specificity
Summary
Macrophages, nonspecific components of the innate immune system, are present in all tissues of the body. During human primary monocyte-macrophage differentiation, PC, PS, and PA species showed a decrease in polyunsaturated fatty acids (PUFA) accompanied by an increase in monounsaturated fatty acids (MUFA) and saturated species (Supplementary Fig. 2b), results that agree with previously reported data[16].
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