title: Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions.
abstract: 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.
  
  
  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.
authors.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine, Charterhouse Square, London EC1M 6BQ, United Kingdom.
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Norling
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Flower
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000818:Animals; D002465:Cell Movement; D004281:Docosahexaenoic Acids / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D044042:Receptors, Formyl Peptide / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D044067:Receptors, Lipoxin / Q000502:physiology
chemical_list: C105101:FPR2 protein, human; C114479:GPR32 protein, human; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D044067:Receptors, Lipoxin; C518399:resolvin D1; D004281:Docosahexaenoic Acids