Krul E S, Tikkanen M J, Cole T G, Davie J M, Schonfeld G
J Clin Invest. 1985 Feb;75(2):361-9. doi: 10.1172/JCI111708.
Apoproteins B and E both interact with cellular low density lipoprotein (LDL) apolipoprotein B and E (apo B,E)-receptors, and very low density lipoproteins (VLDL) contain both apo B and apo E. Our aim was to study the relative importance of apo B and apo E in the binding of VLDL subfractions to cells. Two monoclonal anti-LDL-apo B antibodies (464B1B3 and 464B1B6, 2a and 2b, respectively) and two anti-apo E antibodies (1506 A1.4 and 1907 F6.4) were used to inhibit lipoprotein-cell interactions. In confirmation of previous findings, the binding and degradation of 125I-LDL by human fibroblasts were inhibited approximately 90% by antibodies 2a or 2b or the antigen-binding fragments of 2a, whereas the cellular processing of 125I-VLDL3 (Sf20-60), 125I-VLDL2 (Sf60-120), and 125I-VLDL1 (Sf greater than 120) were inhibited by only approximately 50%, approximately 25%, and less than 10%, respectively. The VLDL1-3 and LDL-dependent intracellular esterification of cholesterol with [3H]oleate were inhibited to a similar extent. Other monoclonal anti-human apo B antibodies inhibited lipoprotein-cell interactions much less effectively and nonimmune IgG isolated from mouse serum did not inhibit at all. 20-fold excesses of LDL produced about the same patterns of inhibition of degradation of 125I-VLDL1-3 and LDL by cells as did antibodies 2a and 2b, whereas homologous unlabeled VLDL1-3 in like amounts inhibited the matched 125I-VLDL subfraction more effectively. Two anti-apo E monoclonal antibodies and a polyclonal anti-apo E antibody inhibited cell-mediated degradation of and lipoprotein-dependent cholesterol esterification by VLDL1 but not VLDL3 or LDL. The results suggest that receptor recognition sites on apo E in preference to sites on apo B mediate the cellular binding of hypertriglyceridemic VLDL1. However, the proportion of particles bound via apo B seems to increase as VLDL decreases in size toward LDL, and virtually all of LDL binding is mediated by apo B.
载脂蛋白B和E均与细胞低密度脂蛋白（LDL）载脂蛋白B和E（apo B、E）受体相互作用，且极低密度脂蛋白（VLDL）同时含有apo B和apo E。我们的目的是研究apo B和apo E在VLDL亚组分与细胞结合中的相对重要性。使用两种抗LDL-apo B单克隆抗体（分别为464B1B3和464B1B6，2a和2b）以及两种抗apo E抗体（1506 A1.4和1907 F6.4）来抑制脂蛋白与细胞的相互作用。正如之前研究所证实的，抗体2a或2b或2a的抗原结合片段可使人类成纤维细胞对125I-LDL的结合及降解受到约90%的抑制，而125I-VLDL3（Sf20 - 60）、125I-VLDL2（Sf60 - 120）和125I-VLDL1（Sf大于120）的细胞处理过程分别仅受到约50%、约25%和小于10%的抑制。VLDL1 - 3和LDL依赖的用[3H]油酸进行的细胞内胆固醇酯化受到的抑制程度相似。其他抗人类apo B单克隆抗体对脂蛋白与细胞相互作用的抑制效果要差得多，从小鼠血清中分离出的非免疫IgG则完全没有抑制作用。20倍过量的LDL对细胞降解125I-VLDL1 - 3和LDL产生的抑制模式与抗体2a和2b产生的大致相同，而等量的同源未标记VLDL1 - 3对匹配的125I-VLDL亚组分的抑制作用更有效。两种抗apo E单克隆抗体和一种抗apo E多克隆抗体抑制了细胞介导的VLDL1降解以及VLDL1依赖的胆固醇酯化，但对VLDL3或LDL没有抑制作用。结果表明，apo E上的受体识别位点而非apo B上的位点介导了高甘油三酯血症性VLDL1与细胞的结合。然而，随着VLDL大小向LDL减小，通过apo B结合的颗粒比例似乎会增加，并且几乎所有LDL的结合都是由apo B介导的。
Zotero 插件