单克隆抗体对兔体内胆固醇酯转运蛋白活性的抑制作用。对脂蛋白组成及高密度脂蛋白胆固醇酯代谢的影响。
Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism.
作者信息
Whitlock M E, Swenson T L, Ramakrishnan R, Leonard M T, Marcel Y L, Milne R W, Tall A R
机构信息
Department of Medicine, Columbia University College of Physicians & Surgeons, New York 10032.
出版信息
J Clin Invest. 1989 Jul;84(1):129-37. doi: 10.1172/JCI114132.
Cholesteryl ester transfer protein (CETP) promotes in vitro transfer of cholesteryl ester (CE) and triglyceride (TG) between lipoproteins. We studied the function of CETP in vivo in rabbit lipoprotein metabolism using a neutralizing monoclonal antibody (MAb, TP1) to CETP. Rabbits were injected with TP1 (n = 8), or irrelevant MAb or saline (control, n = 8), resulting in an initial 71% inhibition of CETP, which fell to 45% after 48 h. HDL CE rose in the inhibited animals, reaching levels that doubled initial and control values at 48 h (P less than 0.001). HDL TG fell reciprocally, but HDL protein did not change, suggesting a CE for TG exchange. VLDL CE/TG decreased. Rabbits were also given [3H]cholesteryl ether HDL (a CE analogue). CETP inhibition delayed the initial clearance of radioactivity from HDL (control 6.8 vs. TP1 4.1 pools/d) and plasma (7.8 vs. 5.2 pools/d). We conclude that CETP plays a quantitatively important role in HDL CE catabolism in the rabbit, promoting the exchange of TG for CE and the clearance of CE from plasma.
胆固醇酯转运蛋白（CETP）可促进脂蛋白间胆固醇酯（CE）和甘油三酯（TG）的体外转运。我们使用针对CETP的中和性单克隆抗体（MAb，TP1）研究了CETP在兔脂蛋白代谢体内的功能。给兔子注射TP1（n = 8）、无关单克隆抗体或生理盐水（对照组，n = 8），导致CETP最初被抑制71%，48小时后降至45%。在受抑制的动物中，高密度脂蛋白胆固醇（HDL CE）升高，在48小时时达到初始值和对照组值的两倍（P小于0.001）。HDL TG相应下降，但HDL蛋白未改变，提示CE与TG发生了交换。极低密度脂蛋白胆固醇（VLDL CE/TG）降低。还给兔子注射了[3H]胆固醇醚HDL（一种CE类似物）。CETP抑制延迟了放射性物质从HDL（对照组6.8 vs. TP1组4.1池/天）和血浆（7.8 vs. 5.2池/天）的初始清除。我们得出结论，CETP在兔HDL CE分解代谢中起重要的定量作用，促进TG与CE的交换以及CE从血浆中的清除。
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