Maresin 1 a Novel Macrophage n‐3 Derived Mediator is a Potent Tissue Regenerative Immunoresolvent

Abstract

Maresins are a novel family of pro‐resolving mediators recently described in self‐resolving inflammatory exudates that are biosynthesized by macrophages (Mϕ). The complete stereochemistry of Maresin 1 (MaR1), the first member of this family to be identified, remained of interest. Here we demonstrate that MaR1 produced by human Mϕ from endogenous DHA matched material obtained by total organic synthesis with stereochemistry 7R,14S‐dihydroxydocosa‐4Z,8E,10E,12Z,16Z,19Z‐hexaenoic acid. We next confirmed the defining potent anti‐inflammatory and pro‐resolving actions of MaR1 with synthetic, demonstrating that MaR1 effectively reduced polymorphonuclear neutrophil infiltration in murine peritonitis and enhanced human Mϕ efferocytosis. At concentrations as low as 10nM, MaR1 accelerated tissue regeneration in surgically injured planaria (Dugesia tigrina). Upon injury planaria were found to biosynthesize MaR1 from deuterium labeled DHA, a process that was inhibited by lipoxygenase inhibitor. These findings demonstrate that MaR1 is a potent immunoresolvent exerting anti‐inflammatory, pro‐resolving and tissue regenerative actions. Moreover, they offer new pathways for assessing macrophage functions and novel mediators in regulating local tissue homeostasis and regeneration.This work was supported by NIH (Grants GM095467 and DE019938)