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Updated: May 29, 2026

A Model of Self-limited Acute Lung Injury by Unilateral Intra-bronchial Acid Instillation
Published on: August 30, 2019
Novel proresolving aspirin-triggered DHA pathway
Charles N Serhan1, Gabrielle Fredman, Rong Yang
1Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. cnserhan@zeus.bwh.harvard.edu
Abstract:
Endogenous mechanisms in the resolution of acute inflammation are of interest because excessive inflammation underlies many pathologic abnormalities. We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. The complete stereochemistry of AT-(NPD1/PD1) proved to be 10R,17R-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. The chirality of hydroxyl groups and geometry of the conjugated triene system essential for bioactivity were established by matching biological materials with stereochemically pure isomers prepared by organic synthesis. AT-(NPD1/PD1) reduced neutrophil (PMN) recruitment in murine peritonitis in a dose-dependent fashion whereby neither a Δ(15)-trans-isomer nor DHA was effective. With human cells, AT-(NPD1/PD1) decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. These results indicate that AT-(NPD1/PD1) is a potent anti-inflammatory proresolving molecule.
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