UPTAKE OF APOLIPOPROTEIN-E-CONTAINING HIGH-DENSITY LIPOPROTEINS BY HEPATIC PARENCHYMAL-CELLS
UPTAKE OF APOLIPOPROTEIN-E-CONTAINING HIGH-DENSITY LIPOPROTEINS BY HEPATIC PARENCHYMAL-CELLS
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DOI：
10.1161/01.atv.4.5.452
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
MAHLEY, RW
中科院分区：
文献类型：
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作者：
FUNKE, H;BOYLES, J;MAHLEY, RW
用琼脂糖柱层析或超速离心法从无胆固醇犬血浆中分离得到的富含载脂蛋白E的高密度脂蛋白(Apo E HDLc)具有基本相同的生化和代谢特性。用这两种方法分离的放射性碘(125I)apo E HDLc具有相同的血浆清除率，即注射剂量的50%在5-10分钟内从血浆中清除，主要是通过肝脏。在正常大鼠和胆固醇喂养的大鼠中，都进行了详细的研究，将载脂蛋白E高密度脂蛋白摄取定位到肝脏内特定类型的细胞。在大鼠中使用犬apo E HDLc的有效性得到了两个物种在血浆清除方面的显著相似之处的观察支持，即，两个物种的快速急性消失期和肝脏对脂蛋白的近乎定量的摄取。犬载脂蛋白E高密度脂蛋白胆固醇(1，1‘’-dioctadecyl-3，3，3‘’，3‘’-tetramethylindocarbocyanine)，荧光标记)注入正常大鼠后，荧光显微镜下可见其主要被实质细胞摄取。光镜放射自显影显示大鼠肝脏对~(125)I apo E HDLc的摄取主要由肝实质细胞进行。同样，胆固醇喂养的大鼠肝脏对载脂蛋白E高密度脂蛋白胆固醇的摄取广泛局限于实质细胞。用碘标记和荧光标记的载脂蛋白E HDLc对正常犬肝小叶进行原位单次灌流，证实脂蛋白的摄取主要由实质细胞进行。肝实质细胞对载脂蛋白E HDLc的血浆清除，即使在胆固醇喂养的动物中，载脂蛋白B，E(LDL)受体显著下调(检测不到)，表明载脂蛋白E受体，可能是残存受体，定位于实质细胞。
Cholesterol-enriched, apolipoprotein E-containing high density lipoproteins (apo E HDLc), which were isolated from the plasma of cholesterol-free dogs by using agarose column chromatography or ultracentrifugation, possessed essentially identical biochemical and metabolic characteristics. Radioiodinated (125I)apo E HDLc isolated by either method gave identical rates of clearance from the plasma, i.e., > 50% of the injected dose was cleared from the plasma within 5-10 minutes, principally by the liver. Detailed studies localizing apo E HDLc uptake to specific cell types within the liver were performed in both normal and cholesterol-fed rats. The validity of using the canine apo E HDLc in the rat was supported by observations of marked similarities in plasma clearance, i.e., a rapid acute phase of disappearance, and a near-quantitative hepatic uptake of lipoproteins in both species. Canine apo E HDLc (fluorescently labeled with 1,1''-dioctadecyl-3,3,3'',3''-tetramethylindocarbocyanine), which were injected into normal rats, appeared to be taken up primarily by parenchymal cells, as determined by fluorescence microscopy. Light microscopic autoradiography also revealed that the uptake of 125I apo E HDLc was principally carried out by parenchymal cells in rat liver. Likewise, the uptake of apo E HDLc by the liver of cholesterol-fed rats was extensively localized to parenchymal cells. An in situ, single-pass perfusion of a lobule of the liver of a normal dog with iodinated and fluorescently labeled apo E HDLc confirmed that the uptake of the lipoproteins was principally carried out by parenchymal cells. The plasma clearance of apo E HDLc by hepatic parenchymal cells, even in cholesterol-fed animals in which the apo B,E (LDL) receptors were markedly down-regulated (undetectable), suggests that the apo E receptor, presumably the remnant receptor, is localized in the parenchymal cells.