Department of Experimental Physiology, University of Athens Medical School, Athens, Greece.
J Lipid Res. 2010 Aug;51(8):2191-201. doi: 10.1194/jlr.M003558. Epub 2010 Mar 23.
Recognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position by lipoprotein associated phospholipase A(2) (Lp-PLA(2)) to lysophosphatidylcholine and small oxidation products. This study examines the involvement of Lp-PLA(2) in the uptake of oxLDL by mouse peritoneal macrophages. LDL with intact Lp-PLA(2) activity [LDL(+)] and LDL with completely inhibited Lp-PLA(2) activity [LDL(-)] were subjected to oxidation with 5 microM CuSO(4) for 6 h [moderately oxLDL (MoxLDL)], or 24 h [heavily oxLDL (HoxLDL)] and peritoneal macrophages were incubated with these preparations. The uptake of MoxLDL(-) was about 30% increased compared with that of MoxLDL(+), and HoxLDL(-) uptake was about 20% increased compared with that of HoxLDL(+). Inhibition of Lp-PLA(2) activity had no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+). Liposomes prepared from the lipid extract of MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+) exhibited a similar pattern to that observed in the uptake of the corresponding intact lipoproteins. This study suggests that the progressive inactivation of Lp-PLA(2) during LDL oxidation leads to an increased uptake of oxLDL by macrophages, which could be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxLDL.
氧化型低密度脂蛋白 (oxLDL) 通过巨噬细胞清道夫受体的识别和摄取以及泡沫细胞的形成，是由氧化修饰的载脂蛋白 B (ApoB) 和 oxLDL 的脂质部分介导的。oxLDL 大量的氧化型磷脂酰胆碱 (oxPC) 在 sn-2 位置被脂蛋白相关磷脂酶 A2 (Lp-PLA2) 水解为溶血磷脂酰胆碱和小的氧化产物。本研究探讨了脂蛋白相关磷脂酶 A2 (Lp-PLA2) 在小鼠腹腔巨噬细胞摄取 oxLDL 中的作用。具有完整 Lp-PLA2 活性的 LDL [LDL(+)] 和完全抑制 Lp-PLA2 活性的 LDL [LDL(-)] 用 5 μM CuSO4 氧化 6 小时[中度氧化 LDL (MoxLDL)]或 24 小时[重度氧化 LDL (HoxLDL)]，并用这些制剂孵育腹腔巨噬细胞。与 MoxLDL(+)相比，MoxLDL(-)的摄取增加了约 30%，与 HoxLDL(+)相比，HoxLDL(-)的摄取增加了约 20%。抑制 Lp-PLA2 活性对 MoxLDL(-)、MoxLDL(+)、HoxLDL(-)和 HoxLDL(+)分离的 ApoB 与 ApoB 脂质体缀合物的摄取没有影响。由 MoxLDL(-)、MoxLDL(+)、HoxLDL(-)和 HoxLDL(+)的脂质提取物制备的脂质体显示出与相应完整脂蛋白摄取观察到的相似模式。本研究表明，LDL 氧化过程中 Lp-PLA2 的逐渐失活导致巨噬细胞对 oxLDL 的摄取增加，这主要归因于 oxLDL 中富含氧化磷脂的脂质部分的摄取增加。
