Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Potent Immunoresolvents

SummaryResolvins are a family of n-3 lipid mediators initially identified in resolving inflammatory exudates that temper inflammatory responses to promote catabasis. Here, temporal metabololipidomics with self-limited resolving exudates revealed that resolvin (Rv) D3 has a distinct time frame from other lipid mediators, appearing late in the resolution phase. Using synthetic materials prepared by stereocontrolled total organic synthesis and metabololipidomics, we established complete stereochemistry of RvD3 and its aspirin-triggered 17R-epimer (AT-RvD3). Both synthetic resolvins potently regulated neutrophils and mediators, reducing murine peritonitis and dermal inflammation. RvD3 and AT-RvD3 displayed leukocyte-directed actions, e.g., blocking human neutrophil transmigration and enhancing macrophage phagocytosis and efferocytosis. These results position RvD3 uniquely within the inflammation-resolution time frame to vantage and contribute to the beneficial actions of aspirin and essential n-3 fatty acids.

Graphical AbstractFigure optionsDownload high-quality image (133 K)Download as PowerPoint slideHighlights
► RvD3 accumulates in late inflammation resolution
► Aspirin triggers biosynthesis of RvD3 17R-epimer (AT-RvD3) that is proresolving
► Complete stereochemistry of RvD3 and AT-RvD3 are established
► RvD3 and AT-RvD3 govern leukocyte functions and local inflammatory responses