Use of monoclonal anti-receptor antibodies to probe the expression of the low density lipoprotein receptor in tissues of normal and Watanabe heritable hyperlipidemic rabbits.
Use of monoclonal anti-receptor antibodies to probe the expression of the low density lipoprotein receptor in tissues of normal and Watanabe heritable hyperlipidemic rabbits.
复制标题
使用单克隆抗受体抗体探测正常兔和渡边遗传性高脂血症兔组织中低密度脂蛋白受体的表达。
DOI：
10.1172/jci111469
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Brown,MS
中科院分区：
文献类型：
--
作者：
Huettinger,M;Schneider,WJ;Ho,YK;Goldstein,JL;Brown,MS
Watanabe遗传性高胆固醇血症（WHHL）兔与患有家族性高胆固醇血症的人类一样，在低密度脂蛋白（LDL）受体中存在遗传缺陷。WHHL成纤维细胞产生受体的低分子量前体形式，其通常不被糖基化并且不以正常速率转运至细胞表面。在目前的研究中，我们使用了一种单克隆抗体，与兔LDL受体的反应，以扩大这些结果，以完整的兔子。我们观察到：（1）正常家兔的肝脏和肾上腺合成高分子量成熟LDL受体，与成纤维细胞相似。(b)在WHHL兔中，肾上腺仅表达低分子量受体前体，肝脏不表达可检测到的受体。(c)当静脉注射时，放射性碘标记的抗LDL受体单克隆抗体在正常家兔中从血浆中清除的速度比在WHHL家兔中快6-10倍，在正常家兔而不是WHHL家兔的肝脏和肾上腺中可证实特异性摄取。后一项发现提出了一种普遍的可能性，即动物或人体内表达的细胞表面受体的总数可以通过测量静脉注射的针对感兴趣受体的单克隆抗体的清除率来估计。图片
Watanabe Heritable Hyperlipidemic (WHHL) rabbits, like humans with familial hypercholesterolemia, have a genetic defect in the low density lipoprotein (LDL) receptor. WHHL fibroblasts produce a low molecular weight precursor form of the receptor that is not glycosylated normally and is not transported to the cell surface at a normal rate. In the current studies, we have used a monoclonal antibody that reacts with the rabbit LDL receptor to extend these findings to intact rabbits. We have made the following observations: (a) In normal rabbits the liver and adrenal glands synthesize high molecular weight mature LDL receptors like those in fibroblasts. (b) In WHHL rabbits the adrenals express only the low molecular weight receptor precursor, and the liver expresses no detectable receptors. (c) When injected intravenously, the radioiodinated anti-LDL receptor monoclonal antibody is cleared from plasma 6-10-fold faster in normal than in WHHL rabbits, with specific uptake demonstrable in livers and adrenals of normal but not WHHL rabbits. The latter finding raises the general possibility that the total number of cell surface receptors expressed by an animal or human in vivo can be estimated by measuring the rate of clearance of an intravenously injected monoclonal antibody directed against the receptor of interest.Images