Biosynthesis of resolvin D1, resolvin D2, and RCTR1 from 7,8(S,S)-epoxytetraene in human neutrophils and macrophages

Significance Statement:
It is now widely appreciated that inflammation contributes to many human conditions that were not thought to involve inflammation, e.g., aging, cardiovascular disease, metabolic syndrome, and neurodegenerative diseases. Uncovering previously unknown processes in human cells that control excessive inflammation is of both general and public health interest. Resolvins are molecules of the body’s own resolution response that stops inflammation and protects organs. It is of broad interest to elucidate biochemical processes that lead to production of these highly potent molecules. Here, using synthetic resolvin 7,8(S,S)-epoxytetraene, we elucidate the central role of this intermediate in human blood cells as a precursor to resolvin D1, D2, and resolvin conjugate in tissue regeneration (RCTR1). These findings provide coordinates necessary for new pro-resolving therapies.