1. Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.193
Figure 2 Biosynthetic pathways leading to the production of specialized proresolving lipid mediators
Figure 2 | Biosynthetic pathways leading to the production of specialized proresolving lipid mediators. a | Lipoxins are biosynthesized in phagocytes from the omega-6 arachidonic acid by direct conversion by arachidonate 15-lipoxygenase (15-LOX) into 15-hydroperoxyeicosatetraenoic acid (15-HpETE), which is subsequently converted to lipoxins by 5-LOX. During platelet–leukocyte interactions leukotriene A4 is then converted by human platelet 12-LOX to lipoxins. The E-series resolvins are biosynthesized from eicosapentaenoic acid (EPA) in a reaction catalysed by acetylated COX2 or CYP450 enzymes. b | The biosynthesis of D-series resolvins and protectins from n-3 docosapentaenoic acid (DPA) is initiated by 15-LOX in humans and 12/15-LOX in mice via 17-lipoxygenation to yield 17S-hydro(peroxy)-7Z,10Z,13Z,15E,19Z-docosapentaenoic acid (17S-HpDPA) which is then converted to either D-series resolvins by 5-LOX or protectins via an epoxyde hydrolase. In human macrophages, n-3 DPA is converted via 14-lipoxygenation to 14S-hydro(peroxy)-7Z,10 Z,12E,16Z,19Z-docosapentaenoic acid (14S-HpDPA), which is the precursor to the biosynthesis of the maresins. In activated endothelial cells, n-3 DPA is converted via 13-LOX to 13(R)-hydro(peroxy)-7Z,10Z,13R,14E,16Z,19Z-docosapentaenoic acid (13R-HpDPA), which can then be donated to neutrophils, by which it is converted to thirteen-series resolvins. In the docosahexaenoic acid (DHA) bioactive metabolome, the biosynthesis of D-series resolvins and protectins is initiated by human 15-LOX to yield 17(S)-HpDHA, which is then converted by 5-LOX to D-series resolvins or protectins. In human macrophages, DHA is converted by 14-lipoxygenation to 14(S)-HpDHA before subsequent conversion to maresins. Aspirin and statin might also jump-start the biosynthesis of several of the proresolving mediator families (see Box 4 for further details).
Perretti, M. et al. (2016) Immune resolution mechanisms in inflammatory arthritis
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