Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

• DOI: 10.1021/acsptsci.3c00201
• Publication Date: 2023-11-20T18:37:26Z
• Authors: Amalie Føreid Rei...; Stephania Libreros; Robert Nshimiyimana; Charles Nicholas ...; Trond Vidar Hansen
• Keywords: efferocytosis

Resolvin E4 (RvE4) belongs to the resolvin family of specialized pro-resolving mediators (SPMs). The resolvins are endogenously formed with both potent and anti-inflammatory biological activities have attracted considerable attention in inflammation research drug discovery. Hence, further metabolism is interest. Gaining knowledge about structure–function metabolites important due their interest drug-discovery efforts. For first time, total synthesis evaluations ω-20 hydroxylated metabolite RvE4, named herein 20-OH-RvE4, presented. RvE4 was converted 20-OH-RvE4 by human polymorphonuclear leukocytes. LC–MS/MS analysis UV spectrophotometry reveal that synthetic matched RvE4-converted product neutrophils. Cellular studies revealed from eicosapentaenoic acid physiologic hypoxia neutrophils macrophages, we established a secondary ω-oxidation A direct comparison actions between its metabolic suggested displayed reduced bioactions stimulating efferocytosis senescent erythrocytes M2-like macrophages. At concentrations down 0.1 nM, increased macrophage erythrophagocytosis, an function diminished transformation. results provided contribute novel molecular insight on local metabolization newest member among SPM superfamily.