Resolvin D1 Limits Polymorphonuclear Leukocytes Recruitment to Inflammatory Loci
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 A4/Annexin-A1 receptor (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 B4. 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.
- resolution of inflammation
- neutrophil/endothelial interaction
- cell trafficking
- omega-3 fatty acids
- docosahexaenoic acid
- Received December 9, 2011.
- Accepted March 29, 2012.
- © 2012 American Heart Association, Inc.