Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions

Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1970-8. doi: 10.1161/ATVBAHA.112.249508. Epub 2012 Apr 12.


Objective: Resolvin D1 (RvD1) limits neutrophil recruitment during acute inflammation and is derived from omega-3 docosahexaenoic acid to promote catabasis. The contribution of its specific receptors, the lipoxin A(4)/Annexin-A1 receptor formyl-peptide receptor 2 (FPR2/ALX) and the orphan receptor G-protein-coupled receptor 32 (GPR32) are of considerable interest.

Methods and results: RvD1 reduced human polymorphonuclear leukocytes recruitment to endothelial cells under shear conditions as quantified using a flow chamber system. Receptor-specific antibodies blocked these anti-inflammatory actions of RvD1, with low (1 nmol/L) concentrations sensitive to GPR32 blockade, while the higher (10 nmol/L) concentration appeared FPR2/ALX-specific. Interestingly, polymorphonuclear leukocytes surface expression of FPR2/ALX but not GPR32 increased following activation with pro-inflammatory stimuli, corresponding with secretory vesicle mobilization. Lipid mediator metabololipidomics carried out with 24-hour exudates revealed that RvD1 in vivo gave a significant reduction in the levels of a number of pro-inflammatory mediators including prostaglandins and leukotriene B(4). These actions of RvD1 were abolished in fpr2 null mice.

Conclusions: Pro-resolving lipid mediators and their receptors, such as RvD1 and the 2 G-protein-coupled receptors, studied here regulate resolution and may provide new therapeutic strategies for diseases with a vascular inflammatory component.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Docosahexaenoic Acids / physiology*
  • Humans
  • Inflammation / pathology*
  • Male
  • Mice
  • Neutrophils / physiology*
  • Receptors, Formyl Peptide / physiology
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Lipoxin / physiology


  • FPR2 protein, human
  • GPR32 protein, human
  • Receptors, Formyl Peptide
  • Receptors, G-Protein-Coupled
  • Receptors, Lipoxin
  • resolvin D1
  • Docosahexaenoic Acids