SPECIFIC HIGH-AFFINITY BINDING OF HIGH-DENSITY LIPOPROTEINS TO CULTURED HUMAN-SKIN FIBROBLASTS AND ARTERIAL SMOOTH-MUSCLE CELLS
SPECIFIC HIGH-AFFINITY BINDING OF HIGH-DENSITY LIPOPROTEINS TO CULTURED HUMAN-SKIN FIBROBLASTS AND ARTERIAL SMOOTH-MUSCLE CELLS
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DOI：
10.1172/jci110797
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
BIERMAN, EL
中科院分区：
文献类型：
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作者：
BIESBROECK, R;ORAM, JF;BIERMAN, EL
用肝素-琼脂糖亲和层析法去除载脂蛋白E和B，研究了人高密度脂蛋白（HDL）与培养的人成纤维细胞和人动脉平滑肌细胞的结合。无载脂蛋白E的125 I-HDL结合的饱和曲线显示至少2个组分：低亲和力不饱和结合和在aptx饱和的高亲和力结合。20 μ g HDL蛋白质/ml。无载脂蛋白E的125 I-HDL与正常成纤维细胞的高亲和力结合的Scatchard分析产生了显著线性的图，指示单一类别的结合位点。125 I-HDL 3和无载脂蛋白E的125 I-HDL与正常成纤维细胞结合的饱和曲线产生显著线性的图，指示单一类别的结合位点。125 I-HDL 3和无载脂蛋白E的125 I-HDL与低密度脂蛋白（LDL）受体阴性成纤维细胞结合的饱和曲线也显示出高亲和力结合，产生线性Scatchard图。在总蛋白质的基础上，HDL 2 HDL 3和极高密度脂蛋白（VHDL）的竞争，有效地为载脂蛋白E-游离HDL结合载脂蛋白E-游离125 I-HDL正常成纤维细胞。另外，HDL 2、HDL 3和VHDL竞争125 I-HDL 3与LDL受体阴性成纤维细胞的结合相似。相反，LDL是HDL结合的弱竞争者。显然，人成纤维细胞和动脉平滑肌细胞都具有特异性高亲和力HDL结合位点。如增强的LDL结合和降解以及增加的固醇合成所示，无载脂蛋白E的HDL 3促进了成纤维细胞的胆固醇流出。这些作用在HDL 3浓度为20 μ g/ml时也达到饱和，表明HDL促进胆固醇流出是通过结合高亲和力细胞表面位点介导的。[血清胆固醇水平与动脉粥样硬化发生风险之间存在很强的负相关性。]
Binding of human high density lipoproteins (HDL) to cultured human fibroblasts and human arterial smooth muscle cells was studied using HDL subjected to heparin-agarose affinity chromatography to remove apoprotein (apo) E and B. Saturation curves for binding of apo E-free 125I-HDL showed at least 2 components: low-affinity nonsaturable binding and high-affinity binding that saturated at .apprx. 20 .mu.g HDL protein/ml. Scatchard analysis of high-affinity binding of apo E-free 125I-HDL to normal fibroblasts yielded plots that were significantly linear, indicative of a single class of binding sites. Saturation curves for binding of both 125I-HDL3 and apo E-free 125I-HDL to normal fibroblasts yielded plots that were significantly linear, indicative of a single class of binding sites. Saturation curves for binding of both 125I-HDL3 and apo E-free 125I-HDL to low density lipoprotein (LDL) receptor-negative fibroblasts also showed high-affinity binding that yielded linear Scatchard plots. On a total protein basis, HDL2 HDL3 and very high density lipoproteins (VHDL) competed as effectively as apo E-free HDL for binding of apo E-free 125I-HDL to normal fibroblasts. Also, HDL2, HDL3, and VHDL competed similarly for binding of 125I-HDL3 to LDL receptor-negative fibroblasts. In contrst, LDL was a weak competitor for HDL binding. Apparently, both human fibroblasts and arterial smooth muscle cells possess specific high affinity HDL binding sites. As indicated by enhanced LDL binding and degradation and increased sterol synthesis, apo E-free HDL3 promoted cholesterol efflux from fibroblasts. These effects also saturated at HDL3 concentrations of 20 .mu.g/ml, suggesting that promotion of cholesterol efflux by HDL is mediated by binding to the high-affinity cell surface sites. [There is a strong inverse correlation between serum cholesterol levels and the risk for development of atherosclerosis.].