title: Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective.
abstract: Unregulated acute inflammation can lead to collateral tissue injury in vital organs, such as the lung during the acute respiratory distress syndrome. In response to tissue injury, circulating platelet-neutrophil aggregates form to augment neutrophil tissue entry. These early cellular events in acute inflammation are pivotal to timely resolution by mechanisms that remain to be elucidated. Here, we identified a previously undescribed biosynthetic route during human platelet-neutrophil interactions for the proresolving mediator maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid). Docosahexaenoic acid was converted by platelet 12-lipoxygenase to 13S,14S-epoxy-maresin, which was further transformed by neutrophils to MaR1. In a murine model of acute respiratory distress syndrome, lipid mediator metabololipidomics uncovered MaR1 generation in vivo in a temporally regulated manner. Early MaR1 production was dependent on platelet-neutrophil interactions, and intravascular MaR1 was organ-protective, leading to decreased lung neutrophils, edema, tissue hypoxia, and prophlogistic mediators. Together, these findings identify a transcellular route for intravascular maresin 1 biosynthesis via platelet-neutrophil interactions that regulates the extent of lung inflammation.
authors.affiliation: Pulmonary and Critical Care Medicine and.
authors.forename: Raja-Elie E
authors.initials: RE
authors.lastname: Abdulnour
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: Pulmonary and Critical Care Medicine and.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Colby
authors.affiliation: Pulmonary and Critical Care Medicine and.
authors.forename: Nandini
authors.initials: N
authors.lastname: Krishnamoorthy
authors.affiliation: Pulmonary and Critical Care Medicine and.
authors.forename: Jack Y
authors.initials: JY
authors.lastname: Timmons
authors.affiliation: Pulmonary and Critical Care Medicine and.
authors.forename: Sook Hwa
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and.
authors.forename: Romain A
authors.initials: RA
authors.lastname: Colas
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089.
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Pulmonary and Critical Care Medicine and Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and blevy@partners.org.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015687:Cell Hypoxia; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D064593:Heterografts; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009504:Neutrophils / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D017713:Platelet Transfusion; D011994:Recombinant Proteins / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013917:Thrombin / Q000494:pharmacology
chemical_list: C000596014:13,14-dihydroxydocosahexaenoic acid; C535211:7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D004281:Docosahexaenoic Acids; D001092:Arachidonate 12-Lipoxygenase; D013917:Thrombin; D006851:Hydrochloric Acid
keywords: inflammation; lung; maresin; platelet; resolution