Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions.
Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions.
复制标题
DOI：
10.1161/atvbaha.112.249508
复制
发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Perretti M
中科院分区：
文献类型：
--
作者：
Norling LV;Dalli J;Flower RJ;Serhan CN;Perretti M
Resolvin D1在急性炎症期间限制中性粒细胞的募集，并来源于omega-3 DHA以促进消退。其特异性受体脂素A4/膜联蛋白a1受体（FPR2/ALX）和孤儿受体GPR32的作用引起了相当大的兴趣。RvD1在剪切条件下减少人PMN向内皮细胞的募集，使用流量室系统进行量化。受体特异性抗体阻断RvD1的抗炎作用，低（1nM）浓度的抗体对GPR32阻断敏感，而高（10nM）浓度的抗体对FPR2/ alx具有特异性。有趣的是，在促炎刺激激活后，PMN表面FPR2/ALX的表达增加，而GPR32的表达不增加，这与分泌囊泡动员相对应。脂质介质代谢脂质组学研究显示，体内RvD1显著降低了包括前列腺素和LTB4在内的多种促炎介质的水平。RvD1的这些作用在fpr2缺失小鼠中被消除。促溶解脂质介质及其受体，如RvD1和本文研究的两种gpcr调节溶解，可能为具有血管炎症成分的疾病提供新的治疗策略。
Resolvin D1 limits neutrophil recruitment during acute inflammation and is derived from omega-3 DHA to promote catabasis. The contribution of its specific receptors, the lipoxin A4/Annexin-A1 receptor (FPR2/ALX) and the orphan receptor GPR32 are of considerable interest. RvD1 reduced human PMN 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 (1nM) concentrations sensitive to GPR32 blockade, whilst the higher (10nM) concentration appeared FPR2/ALX-specific. Interestingly, PMN 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 24h exudates revealed that RvD1 in vivo gave a significant reduction in the levels of a number of pro-inflammatory mediators including prostaglandins and LTB4. These actions of RvD1 were abolished in fpr2 null mice. Pro-resolving lipid mediators and their receptors, such as RvD1 and the two GPCRs studied here regulate resolution and may provide new therapeutic strategies for diseases with a vascular inflammatory component.