title: Resolvin D3 multi-level proresolving actions are host protective during infection.
abstract: Resolution of infection and inflammation is governed by innate immune cells. The resolvin family of n-3 mediators produced by resolving exudates stimulates clearance of neutrophils and attenuates pro-inflammatory signals. Using metabololipidomics, endogenous resolvin D3 (RvD3) was identified in self-resolving exudates during active E. coli infection. Through a new, independent synthetic route for RvD3, we matched endogenous and synthetic RvD3 and determined that RvD3 (ng doses) potently reduced the resolution interval (Ri) by ~4.5h during E. coli peritonitis after administration at peak inflammation (Tmax=12h) and increased leukocyte phagocytosis of E. coli and neutrophils as well as reduced proinflammatory cytokines, chemokines, MMP-2 and MMP-9. At pM-nM concentrations, RvD3 also enhanced human macrophage efferocytosis and bacterial phagocytosis, increased neutrophil bacterial phagocytosis and intracellular ROS generation, and reduced human platelet-PMN aggregation. These results provide additional evidence for potent RvD3 immunoresolvent actions in host defense, host protection and antimicrobial defense.
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: Paul C
authors: PC
authors: Norris
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: Hildur
authors: H
authors: Arnardottir
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: Julia M
authors: JM
authors: Sanger
authors: Cayman Chemical, Ann Arbor, MI 48108, USA.
authors: David
authors: D
authors: Fichtner
authors: Cayman Chemical, Ann Arbor, MI 48108, USA.
authors: Gregory S
authors: GS
authors: Keyes
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. Electronic address: cnserhan@zeus.bwh.harvard.edu.
authors: Charles N
authors: CN
authors: Serhan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000473:pathology; D005231:Fatty Acids, Unsaturated / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010538:Peritonitis / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D005231:Fatty Acids, Unsaturated; C583088:resolvin D3
keywords: Human leukocyte; Infection; Inflammation; Specialized proresolving mediator