Yang, RongFredman, GabrielleKrishnamoorthy, SriramAgrawal, NitinIrimia, DanielPiomelli, DanieleSerhan, Charles2019-10-052011Yang, Rong, Gabrielle Fredman, Sriram Krishnamoorthy, Nitin Agrawal, Daniel Irimia, Daniele Piomelli, and Charles N. Serhan. 2011. “Decoding Functional Metabolomics with Docosahexaenoyl Ethanolamide (DHEA) Identifies Novel Bioactive Signals.” Journal of Biological Chemistry 286 (36): 31532–41. https://doi.org/10.1074/jbc.m111.237990.0021-92581083-351Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483471Neuroinflammation and traumatic brain injury involve activation of inflammatory cells and production of local pro-inflammatory mediators that can amplify tissue damage. Using LC-UV-MS-MS-based lipidomics in tandem with functional screening at the single-cell level in microfluidic chambers, we identified a series of novel bioactive oxygenated docosahexaenoyl ethanolamide( DHEA) derived products that regulated leukocyte motility. These included 10,17-dihydroxydocosahexaenoyl ethanolamide (10,17-diHDHEA) and 15-hydroxy-16(17)-epoxy-docosapentaenoyl ethanolamide (15-HEDPEA), each of which was an agonist of recombinant CB2 receptors with EC50 3.9 X 10(-10) and 1.0 X 10(-10)M. In human whole blood, 10,17-diHDHEA and 15-HEDPEA at concentrations as low as 10 pM each prevented formation of platelet-leukocyte aggregates involving either platelet-monocyte or platelet-polymorphonuclear leukocyte. In vivo, 15-HEDPEA was organ-protective in mouse reperfusion second organ injury. Together these results indicate that DHEA oxidative metabolism produces potent novel molecules with anti-inflammatory and organ-protective properties.en-USJournal Article2019-10-0510.1074/jbc.M111.237990