title: Maresin 1 Biosynthesis and Proresolving Anti-infective Functions with Human-Localized Aggressive Periodontitis Leukocytes.
abstract: Localized aggressive periodontitis (LAP) is a distinct form of early-onset periodontitis linked to periodontal infection with uncontrolled inflammation and leukocyte-mediated tissue destruction. The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPMs). Since the level of the Maresin pathway marker 14-hydroxy-docosahexaenoic acid (14-HDHA) was lower in activated peripheral blood from LAP patients, we investigated the Maresin 1 (MaR1) biosynthetic pathway in these subjects and its role in regulating phagocyte functions. Macrophages from LAP patients had a lower level of expression of 12-lipoxygenase (∼30%) and reduced MaR1 (LAP versus healthy controls [HC], 87.8 ± 50 pg/10(6) cells versus 239.1 ± 32 pg/10(6) cells). Phagocytosis by LAP macrophages was reduced ∼40% compared to that of HC, and killing of periodontal pathogens, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were similarly reduced. LAP neutrophils also displayed slower kinetics (∼30%) and decreased maximal phagocytosis (∼20% lower) with these pathogens than those of HC. The administration of MaR1 at 1 nM enhanced phagocytosis (31 to 65% increase), intracellular antimicrobial reactive oxygen species production (26 to 71% increase), bacterial killing of these periodontal pathogens (22 to 38% reduction of bacterial titers), and restored impairment of LAP phagocytes. Together, these results suggest that therapeutics targeting the Maresin pathway have clinical utility in treating LAP and other oral diseases associated with infection, inflammation, and altered phagocyte functions.
authors.affiliation: 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, Massachusetts, USA Division of Periodontology, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA Department of Periodontology, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Chin-Wei
authors.initials: CW
authors.lastname: Wang
authors.affiliation: 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, Massachusetts, USA.
authors.forename: Romain A
authors.initials: RA
authors.lastname: Colas
authors.affiliation: 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, Massachusetts, USA.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: 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, Massachusetts, USA.
authors.forename: Hildur H
authors.initials: HH
authors.lastname: Arnardottir
authors.affiliation: Department of Periodontology, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Department of Periodontology, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.affiliation: 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, Massachusetts, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Chiang
authors.affiliation: Division of Periodontology, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA Department of Periodontology, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
authors.affiliation: 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, Massachusetts, USA Division of Periodontology, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA cnserhan@zeus.bwh.harvard.edu.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology; D010520:Aggressive Periodontitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D010587:Phagocytosis; D016966:Porphyromonas gingivalis / Q000502:physiology
chemical_list: C535211:7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid; D004281:Docosahexaenoic Acids; D001092:Arachidonate 12-Lipoxygenase