title: Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents.
abstract: Resolvins 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.
authors: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Jesmond
authors: J
authors: Dalli
authors: Jeremy W
authors: JW
authors: Winkler
authors: Romain A
authors: RA
authors: Colas
authors: Hildur
authors: H
authors: Arnardottir
authors: Chien-Yee C
authors: CY
authors: Cheng
authors: Nan
authors: N
authors: Chiang
authors: Nicos A
authors: NA
authors: Petasis
authors: Charles N
authors: CN
authors: Serhan
mesh_terms: D000818:Animals; D001241:Aspirin / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000276:immunology; D055442:Metabolome; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000188:drug therapy; D010587:Phagocytosis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; C114479:GPR32 protein, human; D007166:Immunosuppressive Agents; D043562:Receptors, G-Protein-Coupled; C583088:resolvin D3; D001241:Aspirin