title: Resolvin E2 formation and impact in inflammation resolution.
abstract: Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1-10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein-coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (K(d) 24.7 ± 10.1 nM) and resolvin E1 activation of recombinant G-protein-coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sungwhan F
authors.initials: SF
authors.lastname: Oh
authors.forename: Maria
authors.initials: M
authors.lastname: Dona
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Fredman
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnamoorthy
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000818:Animals; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D010972:Platelet Activating Factor / Q000276:immunology / Q000378:metabolism
chemical_list: D016023:Integrins; D010972:Platelet Activating Factor; C517406:resolvin E2; D015118:Eicosapentaenoic Acid