Abdulnour, Raja-ElieDalli, JesmondColby, JenniferKrishnamoorthy, NandiniTimmons, JackTan, Sook HwaColas, RomainPetasis, NicosSerhan, CharlesLevy, Bruce2019-10-052014Abdulnour, Raja-Elie E., Jesmond Dalli, Jennifer K. Colby, Nandini Krishnamoorthy, Jack Y. Timmons, Sook Hwa Tan, Romain A. Colas, Nicos A. Petasis, Charles N. Serhan, and Bruce D. Levy. 2014. “Maresin 1 Biosynthesis during Platelet–neutrophil Interactions Is Organ-Protective.” Proceedings of the National Academy of Sciences 111 (46): 16526–31. https://doi.org/10.1073/pnas.1407123111.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483447Unregulated 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.en-USJournal Article2019-10-0510.1073/pnas.1407123111