title: Identification and Actions of a Novel Third Maresin Conjugate in Tissue Regeneration: MCTR3.
abstract: Maresin conjugates in tissue regeneration (MCTR) are a new family of evolutionarily conserved chemical signals that orchestrate host responses to promote tissue regeneration and resolution of infections. Herein, we identified the novel MCTR3 and established rank order potencies and matched the stereochemistries of MCTR1, MCTR2 and MCTR3 using material prepared by total organic synthesis and mediators isolated from both mouse and human systems. MCTR3 was produced from endogenous substrate by E. coli activated human macrophages and identified in sepsis patients. Each of the three synthetic MCTR dose-dependently (1-100 nM) accelerated tissue regeneration in planaria by 0.6-0.9 days. When administered at the onset or peak of inflammation, each of the MCTR promoted resolution of E. coli infections in mice. They increased bacterial phagocytosis by exudate leukocytes (~15-50%), limited neutrophil infiltration (~20-50%), promoted efferocytosis (~30%) and reduced eicosanoids. MCTR1 and MCTR2 upregulated human neutrophil and macrophage phagocytic responses where MCTR3 also proved to possess potent actions. These results establish the complete stereochemistry and rank order potencies for MCTR1, MCTR2 and MCTR3 that provide novel resolution moduli in regulating host responses to clear infections and promote tissue regeneration.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Sanger
authors.affiliation: Department of Cell Biology, Rowan University - SOM, Stratford, New Jersey, United States of America.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Rodriguez
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Nan
authors.initials: N
authors.lastname: Chiang
authors.affiliation: Department of Cell Biology, Rowan University - SOM, Stratford, New Jersey, United States of America.
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Spur
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010932:Planarians / Q000187:drug effects / Q000502:physiology; D012038:Regeneration / Q000187:drug effects; D018805:Sepsis / Q000097:blood / Q000382:microbiology
chemical_list: D000893:Anti-Inflammatory Agents; D004281:Docosahexaenoic Acids