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dc.contributor.authorDalli, Jesmond
dc.contributor.authorVlasakov, Iliyan
dc.contributor.authorRiley, Ian
dc.contributor.authorRodriguez, Ana
dc.contributor.authorSpur, Bernd
dc.contributor.authorPetasis, Nicos
dc.contributor.authorChiang, Nan
dc.contributor.authorSerhan, Charles
dc.date.accessioned2019-10-05T16:05:03Z
dc.date.issued2016
dc.identifier.citationDalli, Jesmond, Iliyan Vlasakov, Ian R. Riley, Ana R. Rodriguez, Bernd W. Spur, Nicos A. Petasis, Nan Chiang, and Charles N. Serhan. 2016. “Maresin Conjugates in Tissue Regeneration Biosynthesis Enzymes in Human Macrophages.” Proceedings of the National Academy of Sciences 113 (43): 12232–37. https://doi.org/10.1073/pnas.1607003113.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483489*
dc.description.abstractMacrophages are central in coordinating immune responses, tissue repair, and regeneration, with different subtypes being associated with inflammation-initiating and proresolving actions. We recently identified a family of macrophage-derived proresolving and tissue regenerative molecules coined maresin conjugates in tissue regeneration (MCTR). Herein, using lipid mediator profiling we identified MCTR in human serum, lymph nodes, and plasma and investigated MCTR biosynthetic pathways in human macrophages. With human recombinant enzymes, primary cells, and enantiomerically pure compounds we found that the synthetic maresin epoxide intermediate 13S,14S-eMaR (13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid) was converted to MCTR1 (13R-glutathionyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) by LTC4S and GSTM4. Incubation of human macrophages with LTC4S inhibitors blocked LTC4 and increased resolvins and lipoxins. The conversion of MCTR1 to MCTR2 (13R-cysteinylglycinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) was catalyzed by.-glutamyl transferase (GGT) in human macrophages. Biosynthesis of MCTR3 was mediated by dipeptidases that cleaved the cysteinyl-glycinyl bond of MCTR2 to give 13R-cysteinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid. Of note, both GSTM4 and GGT enzymes displayed higher affinity to 13S, 14S-eMaR and MCTR1 compared with their classic substrates in the cysteinyl leukotriene metabolome. Together these results establish the MCTR biosynthetic pathway and provide mechanisms in tissue repair and regeneration.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleMaresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorSerhan, Charles Nicholas::40628494470cc50c44bd3fc1053e7d94::600
dc.date.available2019-10-05T16:05:03Z
dash.workflow.comments1Science Serial ID 91378
dc.identifier.doi10.1073/pnas.1607003113
dash.source.volume113;43
dash.source.page12232


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