A potent proresolving mediator 17R-resolvin D2 from human macrophages, monocytes, and saliva

Sci Adv. 2024 Nov 22;10(47):eadq4785. doi: 10.1126/sciadv.adq4785. Epub 2024 Nov 20.

Abstract

Production of specialized proresolving mediators (SPMs) during the resolution phase in the acute inflammatory response is key to orchestrating complete resolution. Here, we uncovered a trihydroxy resolvin in fresh human saliva. We identified and determined its complete stereochemistry as 7S,16R,17R-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (17R-RvD2) using total organic synthesis and matching of physical properties. The 17R-RvD2 was produced by activated human M2-like macrophages, M1-like macrophages, and human peripheral blood monocytes. 17R-RvD2 displayed potent proresolving functions (picomolar to nanomolar). Topical application of 17R-RvD2 on mouse ear skin reduced neutrophilic infiltration (~50%). 17R-RvD2 increased M2 markers CD206 and CD163 on human monocyte-derived macrophages and enhanced efferocytosis of senescent red blood cells by M2-like macrophages (EC50 ~ 2.6 × 10-14 M). In addition, 17R-RvD2 activated the RvD2 receptor and was equipotent to its epimer RvD2. 17R-RvD2 also significantly increased phagocytosis of Escherichia coli by human neutrophils. Together, these results establish the complete stereochemistry and potent proresolving functions of the previously unknown 17R-RvD2.

MeSH terms

  • Animals
  • Docosahexaenoic Acids* / chemistry
  • Docosahexaenoic Acids* / metabolism
  • Docosahexaenoic Acids* / pharmacology
  • Humans
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Mice
  • Monocytes* / drug effects
  • Monocytes* / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Phagocytosis / drug effects
  • Saliva* / metabolism

Substances

  • Docosahexaenoic Acids
  • resolvin D2