2. Academic Validation
  3. Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance

Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance

  • Sci Rep. 2016 Jan 8:6:18972. doi: 10.1038/srep18972.
Jeremy W Winkler 1,  Sarah K Orr 1,  Jesmond Dalli 1,  Chien-Yee C Cheng 1,  Julia M Sanger 1,  Nan Chiang 1,  Nicos A Petasis 2,  Charles N Serhan 1
Affiliations

Affiliations

  • 1 Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 USA.
  • 2 Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California 90089 USA.
PMID: 26743932 DOI: 10.1038/srep18972
Abstract

Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular response by orchestrating resolution networks involved in host responses to injury and Infection. Here, endogenous resolvin D4 was identified in human tissues and found to persist late into the resolution phase of acute murine Staphylococcus aureus infections. Completion of the first total synthesis of resolvin D4 established the absolute stereochemical configuration of RvD4 confirmed by matching with endogenous RvD4 from resolving exudates in dorsal pouch S. aureus infections. In vivo, RvD4 (ng/mouse) reduced neutrophilic infiltration (~40%) and enhanced uptake of apoptotic PMN (51%) by human dermal fibroblasts at concentrations as low as 0.1 nM. These results establish the complete stereochemistry of RvD4 as 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid and its novel pro-resolving actions in S. aureus infections as well as its potent ability to stimulate clearance of apoptotic cells by skin fibroblasts.

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