Cell-cell interaction in the transcellular biosynthesis of novel omega-3-derived lipid mediators

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) display beneficial actions in human diseases. The molecular basis for these actions remains of interest. We recently identified novel mediators generated from omega-3 PUFA during cell-cell interactions that displayed potent anti-inflammatory and proresolving actions. Compounds derived from EPA are designated resolvins of the E series (RvE1), and those biosynthesized from DHA are denoted resolvins of the D series (RvD) and docosatriene, such as protectin D1 (PD1), which belongs to the family of protectins. In addition, treatment using aspirin initiates a related epimeric series by triggering endogenous formation of the 17R-RvD series, denoted as aspirin-triggered (AT)-RvDs. These compounds possess potent anti-inflammatory actions in vivo that essentially are equivalent to their counterpart generated without aspirin, namely the 17S-RvDs. In this chapter, we provide an overview and detail protocols of the biosynthesis and bioactions of these newly uncovered pathways and products that include three distinct series: 18R-resolvins of the E series derived from EPA (i.e., RvE1); 17R-resolvins of the D series from DHA (AT-RvD1 through RvD4); and 17S-resolvins of the D series from DHA (RvD1 through RvD4).