Phagocytosis of aggregated lipoprotein by macrophages: low density lipoprotein receptor-dependent foam-cell formation.
Phagocytosis of aggregated lipoprotein by macrophages: low density lipoprotein receptor-dependent foam-cell formation.
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巨噬细胞对聚集脂蛋白的吞噬作用：低密度脂蛋白受体依赖性泡沫细胞形成。
DOI：
10.1073/pnas.86.8.2713
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发表时间：
1989
影响因子：
11.1
通讯作者：
Heinecke,JW
中科院分区：
文献类型：
--
作者：
Suits,AG;Chait,A;Aviram,M;Heinecke,JW
通过与磷脂酶 C (PLC-LDL) 一起孵育而修饰的低密度脂蛋白 (LDL) 在溶液中聚集，并被人类和小鼠巨噬细胞快速吸收和降解，在体外产生泡沫细胞。人、小鼠和兔巨噬细胞降解 125I 标记的 PLC-LDL (125I-PLC-LDL) 的速度比天然 125I 标记的 LDL (125I-LDL) 的速度快，而非吞噬细胞（例如人成纤维细胞和牛主动脉内皮细胞）降解 125I-PLC-LDL 的速度比 125I-LDL 慢。这表明PLC-LDL的内化机制是吞噬作用。通过电子显微镜检查，小鼠腹腔巨噬细胞似乎正在吞噬 PLC-LDL。人巨噬细胞对 125I-PLC-LDL 的摄取和降解被杂交瘤 C7 产生的单克隆抗体 C7 (IgG2b) 抑制超过 80%，该抗体阻断 LDL 受体的配体结合结构域。同样，在用磷脂酶 C 处理之前，125I-LDL (125I-MeLDL) 的甲基化可使其随后被人类巨噬细胞的摄取和降解减少 90% 以上。巨噬细胞对磷脂酶 C 修饰的 125I-MeLDL 的摄取和降解可以通过将甲基化脂蛋白与载脂蛋白 E（LDL 受体识别的配体）一起孵育来恢复。这些结果表明巨噬细胞通过LDL受体依赖性吞噬作用内化PLC-LDL。
Low density lipoprotein (LDL) modified by incubation with phospholipase C (PLC-LDL) aggregates in solution and is rapidly taken up and degraded by human and mouse macrophages, producing foam cells in vitro. Human, mouse, and rabbit macrophages degraded 125I-labeled PLC-LDL (125I-PLC-LDL) more rapidly than native 125I-labeled LDL (125I-LDL), while nonphagocytic cells such as human fibroblasts and bovine aortic endothelial cells degraded 125I-PLC-LDL more slowly than 125I-LDL. This suggested the mechanism for internalization of PLC-LDL was phagocytosis. When examined by electron microscopy, mouse peritoneal macrophages appeared to be phagocytosing PLC-LDL. The uptake and degradation of 125I-PLC-LDL by human macrophages was inhibited greater than 80% by the monoclonal antibody C7 (IgG2b) produced by hybridoma C7, which blocks the ligand binding domain of the LDL receptor. Similarly, methylation of 125I-LDL (125I-MeLDL) prior to treatment with phospholipase C decreased its subsequent uptake and degradation by human macrophages by greater than 90%. The uptake and degradation of phospholipase C-modified 125I-MeLDL by macrophages could be restored by incubation of the methylated lipoprotein with apoprotein E, a ligand recognized by the LDL receptor. These results indicate that macrophages internalize PLC-LDL by LDL receptor-dependent phagocytosis.