Resolvin D2 restores neutrophil directionality and improves survival after burns

Tomohiro Kurihara, Caroline N. Jones, Yong Ming Yu, Alan J. Fischman, Susumu Watada, Ronald G. Tompkins, Shawn P. Fagan, Daniel Irimia

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Following severe burns and trauma injuries, the changes of neutrophil migratory phenotype are a double-edged sword. Activated neutrophils migrate into injured tissues and help contain microbial infections, but they can also enter normal tissues and damage vital organs. Depleting the neutrophils from circulation protects vital organs against neutrophilinduced damage but leaves the body exposed to infectious complications. Here we show that restoring normal neutrophil migratory phenotype in rats with burn injuries correlates with improved survival in a classical double-injury model of sequential burn and septic insults. We uncovered that the directionality of neutrophils from burned rats can be restored both in vitro by 1 nM resolvin D2 (RvD2) and in vivo by RvD2 for 7 d, 25 ng/kg body mass (8-10 ng/rat). Restoring neutrophil directionality dramatically increases survival after a second septic insult at d 9 postburn. Survival of RvD2- treated animals increases from 0 to 100% after lipopolysaccharide injection and is extended by 1 wk after cecal ligation. Survival does not significantly increase when the restoration of neutrophil directionality is incomplete, following shorter regimens of RvD2. We conclude that restoring neutrophil directionality using RvD2 could have prophylactic value and delay lethal complications after burn injuries.

Original languageEnglish
Pages (from-to)2270-2281
Number of pages12
JournalFASEB Journal
Volume27
Issue number6
DOIs
Publication statusPublished - 2013 Jun

Keywords

  • Chemotaxis
  • Inflammation
  • Innate immunity
  • Lipid mediators
  • Microfluidics

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Kurihara, T., Jones, C. N., Yu, Y. M., Fischman, A. J., Watada, S., Tompkins, R. G., Fagan, S. P., & Irimia, D. (2013). Resolvin D2 restores neutrophil directionality and improves survival after burns. FASEB Journal, 27(6), 2270-2281. https://doi.org/10.1096/fj.12-219519