Intra- and trans-cellular mechanisms for biosynthesis of lipid-derived mediators during acute and resolving stages of inflammation. During the inflammatory response, specific enzymes such as 5-LOX, 15-LOX, and COX-2 are involved in the generation of pro- and anti-inflammatory lipid mediators in different cell types. Pro-inflammatory lipid mediators—HXA3, LTB4, andPGE2—are synthesized intracellularly. Anti-inflammatory lipid mediators are produced via intermediatemetabolites transferred from cell to cell to complete the synthesis. Transcellular biosynthesis is important for the generation of several COX and 5-LOX metabolites such as RvE1 and RvE2 as well as lipid mediators synthesized by several LOX enzymes (LXA3 and resolvins: RvD1, RvD2, RvD3, and RvD4)