E-series resolvins
RvE is a di- or tri-hydroxyl metabolite of EPA. To date, four RvEs (RvE1, 18S-RvE1, RvE2, and RvE3) have been discovered. COX-2, acetylated by aspirin in hypoxic endothelial cells, introduces oxygen groups into 18R-hydro (peroxy)-eicosapentaenoic acid (18R-HEPE). Activated PMN uses 5-LOX to convert 18R-HEPE to 5S (6)-epoxy-18R-HEPE, which is further hydrolyzed to RvE1 (Serhan et al. 2000).
RvE2 is produced by reduction of 18R HEPE products by 5-LOX to 5S-hydroperoxy, 18-hydroxy-EPE in whole blood (Oh et al. 2012). Unlike RvE1, RvE2 and RvE3 are biosynthesized from 18-HEPE via the 12/15-LOX pathway in eosinophils (Isobe et al. 2012b). Endogenous RvE1 has been shown to accumulate for between 48 and 72 hours, which is a delayed time point of inflammation (Hong et al. 2008). RvE2 appeared at the time point corresponding to initial PMN infiltration in rat peritoneal exudate stimulated by zymosan A and decreased within 24 hours (Isobe et al. 2012a). 18S-RvE1 is produced by 5-LOX and LTA4 hydrolase using 18S-HEPE as a substrate (Oh et al. 2011).