Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Arterioscler Thromb Vasc Biol. 2011 Jun;31(6):1333-41. doi: 10.1161/ATVBAHA.111.226258. Epub 2011 Apr 7.
Neutrophils play a key role in the immune response but can undesirably exacerbate inflammation. High-density lipoproteins (HDL) are antiinflammatory particles, exerting beneficial cardiovascular influences. We determined whether HDL exerts antiinflammatory effects on neutrophils and explored the mechanisms by which these occur.
CD11b on activated human neutrophils was significantly attenuated by apolipoprotein A-I (apoA-I) and HDL. The effects of apoA-I were mediated via ABCA1, whereas the effects of HDL were via scavenger receptor BI. Both were associated with a reduction in the abundance of lipid rafts, and a strong correlation between raft abundance and CD11b activation was observed. ApoA-I and HDL reduced neutrophil adhesion to a platelet monolayer under shear flow, as well as neutrophil spreading and migration. ApoA-I also inhibited leukocyte recruitment to the endothelium in an acute in vivo model of inflammation. Finally, infusion of reconstituted HDL in patients with peripheral vascular disease was demonstrated to significantly attenuate neutrophil activation.
We describe here a novel role for HDL and apoA-I in regulating neutrophil activation using in vitro, in vivo, and clinical approaches. We also show that these effects of HDL and apoA-I involve a mechanism requiring changes in membrane domain content rather than in cholesterol efflux per se.
中性粒细胞在免疫反应中发挥关键作用，但可能不当地加剧炎症。高密度脂蛋白（HDL）是抗炎颗粒，对心血管具有有益影响。我们确定 HDL 是否对中性粒细胞发挥抗炎作用，并探讨了发生这些作用的机制。
激活的人中性粒细胞上的 CD11b 明显被载脂蛋白 A-I（apoA-I）和 HDL 减弱。apoA-I 的作用是通过 ABCA1 介导的，而 HDL 的作用是通过清道夫受体 BI 介导的。两者均与脂筏丰度的降低有关，并且观察到筏丰度与 CD11b 活化之间存在很强的相关性。apoA-I 和 HDL 可减少剪切流下中性粒细胞与血小板单层的黏附，以及中性粒细胞的扩展和迁移。apoA-I 还抑制了急性炎症体内模型中白细胞向内皮的募集。最后，在周围血管疾病患者中输注重建的 HDL 被证明可显著减弱中性粒细胞的活化。
我们在这里使用体外、体内和临床方法描述了 HDL 和 apoA-I 调节中性粒细胞活化的新作用。我们还表明，HDL 和 apoA-I 的这些作用涉及一种需要改变膜域含量的机制，而不是胆固醇流出本身。
