PHENOTYPES OF APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E AFTER LIVER-TRANSPLANTATION
PHENOTYPES OF APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E AFTER LIVER-TRANSPLANTATION
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DOI：
10.1172/jci115288
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发表时间：
1991-07-01
影响因子：
15.9
通讯作者：
YOUNG, SG
中科院分区：
文献类型：
--
作者：
LINTON, MF;GISH, R;YOUNG, SG
载脂蛋白（apo）E以及两种B载脂蛋白，即apoB48和apoB100，是人类脂蛋白代谢中的重要蛋白质。apoE和apoB基因中常见的多态性导致氨基酸替换，使这些蛋白质产生易于检测的表型差异。我们研究了肝移植前后apoE和apoB表型的变化，以获得对载脂蛋白生理学的新见解。在我们研究的所有29名患者中，通过等电聚焦评估，受者术后血清apoE表型几乎完全转变为供者的表型，这提供了证据表明血浆中超过90%的apoE是由肝脏合成的。相比之下，肝移植后脑脊液apoE表型没有转变为供者的表型，这表明脑脊液中的大多数apoE不能来自血浆池，因此必定是在局部合成的。apoB100表型（使用单克隆抗体MB19通过免疫测定评估，MB19是一种检测apoB中双等位基因多态性的抗体）总是转变为供者的表型。在4名血脂正常的患者中，我们测定了在富含脂肪的餐后3小时从血浆中分离出的“乳糜微粒部分”中apoB100和apoB48的MB19表型。有趣的是，乳糜微粒部分中的apoB100总是具有供者的表型，这表明在富含脂肪的餐后出现在血浆中的绝大多数大的、富含甘油三酯的含apoB100的脂蛋白实际上是肝脏来源的极低密度脂蛋白。肝移植后血浆乳糜微粒部分中apoB48的MB19表型没有改变，这表明血浆乳糜微粒中几乎所有的apoB48都来自肠道。这些结果与我们对器官供者肠道活检标本的免疫细胞化学研究结果一致；使用apoB特异性单克隆抗体，我们在供者肠道活检标本中发现了apoB48的证据，但没有发现apoB100的证据。
Apolipoprotein (apo) E and the two B apolipoproteins, apoB48 and apoB100, are important proteins in human lipoprotein metabolism. Commonly occurring polymorphisms in the genes for apoE and apoB result in amino acid substitutions that produce readily detectable phenotypic differences in these proteins. We studied changes in apoE and apoB phenotypes before and after liver transplantation to gain new insights into apolipoprotein physiology. In all 29 patients that we studied, the postoperative serum apoE phenotype of the recipient, as assessed by isoelectric focusing, converted virtually completely to that of the donor, providing evidence that > 90% of the apoE in the plasma is synthesized by the liver. In contrast, the cerebrospinal fluid apoE phenotype did not change to the donor's phenotype after liver transplantation, indicating that most of the apoE in CSF cannot be derived from the plasma pool and therefore must be synthesized locally. The apoB100 phenotype (assessed with immunoassays using monoclonal antibody MB19, an antibody that detects a two-allele polymorphism in apoB) invariably converted to the phenotype of the donor. In four normolipidemic patients, we determined the MB19 phenotype of both the apoB100 and apoB48 in the "chylomicron fraction" isolated from plasma 3 h after a fat-rich meal. Interestingly, the apoB100 in the chylomicron fraction invariably had the phenotype of the donor, indicating that the vast majority of the large, triglyceride-rich apoB100-containing lipoproteins that appear in the plasma after a fat-rich meal are actually VLDL of hepatic origin. The MB19 phenotype of the apoB48 in the plasma chylomicron fraction did not change after liver transplantation, indicating that almost all of the apoB48 in plasma chylomicrons is derived from the intestine. These results were consistent with our immunocytochemical studies on intestinal biopsy specimens of organ donors; using apoB-specific monoclonal antibodies, we found evidence for apoB48, but not apoB100, in donor intestinal biopsy specimens.