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Resolvin E4 (RvE4) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1 It is produced from eicosapentaenoic acid by 15-lipoxygenase (15-LO) via 15(S)-HpEPE and 15S-hydroxy, 5S-HpEPE intermediates in vitro and by isolated human M2 macrophages or polymorphonuclear (PMN) neutrophils under normoxic or hypoxic conditions. RvE4 synthesis is enhanced in M2 macrophage and neutrophil co-cultures, indicating transcellular biosynthesis by a potential 15-LO and 5-LO mechanism. It has been found in mouse inflammatory exudates. RvE4 (10 nM) increases efferocytosis of apoptotic neutrophils or senescent red blood cells (sRBCs) by human M2 macrophages under hypoxic conditions in vitro. Intraperitoneal administration of RvE4 (100 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of hemorrhagic peritonitis induced by zymosan A and thrombin. It also increases inflammatory exudate macrophage infiltration and efferocytosis of apoptotic neutrophils and/or RBCs in the same model.

1.Norris, P.C., Libreros, S., and Serhan, C.N.Resolution metabolomes activated by hypoxic environmentSci. Adv.5(10)eaax4895(2019)

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