Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.
Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.
复制标题
磷脂脂质体在致动脉粥样硬化的血浆中获得载脂蛋白E并阻止培养的巨噬细胞的胆固醇负荷。
DOI：
10.1172/jci112975
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Brocia,R
中科院分区：
文献类型：
--
作者：
Williams,KJ;Tall,AR;Bisgaier,C;Brocia,R
单次输注磷脂脂质体即可迅速且持久地消除高胆固醇兔血浆在培养的巨噬细胞中引起胆固醇酯负荷的能力。这种血浆磷脂富集引起了细胞胆固醇流出的中度刺激，并且出人意料地几乎完全抑制了细胞对β-极低密度脂蛋白（β-VLDL）的摄取，β-极低密度脂蛋白是高胆固醇兔血浆中主要富含胆固醇酯的颗粒。细胞活力和低密度脂蛋白受体活性不受影响。脂质体与 β-VLDL 一起孵育导致载脂蛋白 E (apoE) 转移至脂质体；然后重新分离的apoE-磷脂脂质体有效地竞争细胞脱辅基蛋白受体。因此，磷脂输注导致培养的巨噬细胞中胆固醇酯积累减少的主要机制是阻断细胞对 β-VLDL 的摄取。脂质体消耗 apoE 的 β-VLDL，然后竞争受体介导的摄取。这些结果表明，一种新的机制有助于磷脂输注的已知抗动脉粥样硬化作用：输注的脂质体获得 apoE，然后阻止动脉壁巨噬细胞对致动脉粥样硬化脂蛋白的摄取。
A single infusion of phospholipid liposomes promptly and persistently abolished the ability of hypercholesterolemic rabbit plasma to cause cholesteryl ester loading in cultured macrophages. This phospholipid enrichment of plasma caused moderate stimulation of cellular cholesterol efflux and, unexpectedly, almost complete inhibition of cellular uptake of beta-very low density lipoprotein (beta-VLDL), the major cholesteryl ester-rich particle in hypercholesterolemic rabbit plasma. Cell viability and LDL receptor activity were unaffected. Incubation of liposomes with beta-VLDL resulted in transfer of apolipoprotein-E (apoE) to the liposomes; reisolated apoE-phospholipid liposomes then competed efficiently for cellular apoprotein receptors. Thus, a major mechanism by which phospholipid infusions result in diminished accumulation of cholesteryl ester in cultured macrophages is by blocking cellular uptake of beta-VLDL. The liposomes deplete beta-VLDL of apoE, then compete for receptor-mediated uptake. These results suggest a novel mechanism contributing to the known antiatherogenic effect of phospholipid infusions: infused liposomes acquire apoE, then block uptake of atherogenic lipoproteins by arterial wall macrophages.Images