Eicosanoid production by macrophages during inflammation depends on the M1/M2 phenotype

Abstract

Macrophages are important in inflammation, and are involved in many physiological and pathological processes. Additionally, macrophages are important producers of eicosanoids, lipids that influence the inflammatory response. Our study aimed to explore the role of eicosanoids in the inflammatory response by studying the production of eicosanoids by macrophages on different stages of inflammation. Murine peritoneal macrophages (MPMs) were obtained at different stages of inflammation, which were then cultured in vitro with polyunsaturated fatty acids. Eicosanoids in MPMs were then detected by liquid chromatography–mass spectrometry. The metabolites derived from the cyclooxygenase (COX) pathway were increased, whereas those from the lipoxygenase (LOX) pathway were reduced. Additionally, the ratio of arachidonic acid (AA)-derived and eicosapentaenoic acid (EPA)-derived eicosanoids was dependent on the stage of inflammation. Moreover, the composition of macrophages with different phenotypes changed. To clarify the relationship between the phenotypes of macrophages and eicosanoids metabolism, we detected the eicosanoids in M1 and M2 differentiated THP-1 cells. Overall, M1 preferred AA, whereas M2 preferred EPA as substrate, which was related to the expression of COX and LOX. In conclusion, this study demonstrates that the difference in macrophage eicosanoids metabolism during the inflammatory response is related to the macrophage polarisation.