Stoffel W, Demant T
Proc Natl Acad Sci U S A. 1981 Jan;78(1):611-5. doi: 10.1073/pnas.78.1.611.
Studies were undertaken to determine the applicability and effectiveness of immunoadsorption chromatography on anti-low density lipoprotein (LDL) columns as a plasma-cholesterol-lowering procedure. Mass production and isolation of monospecific antibodies against swine LDL (rho = 1.006-1.063 g/ml) was carried out by immunization of sheep with swine LDL and selective antibody adsorption from their antisera by chromatography on LDL-Sepharose. The isolated LDL antibodies were then covalently linked to Sepharose CL-4B. Pig plasma LDL was effectively removed in vitro by the anti-LDL-Sepharose beads. In vivo studies were performed in pigs with (i) a plasma-separator membrane permeable to solutes below Mr 2,000,000 or (ii) a blood centrifuge interposed into an arteriovenous shunt to separate the corpuscular elements of blood from the plasma. In either case, the plasma was passed through the anti-LDL-Sepharose column and recirculated into the venous part of the shunt. Plasma cholesterol levels were reduced 70-80% by this procedure and rebounded 3-4 days after the extracorporeal immunoadsorption procedure. This continuous plasma separation-immunoadsorption procedure may have broad applicability for the elimination of any plasma component with antigenic properties.
开展了多项研究,以确定抗低密度脂蛋白(LDL)柱上的免疫吸附色谱法作为一种降低血浆胆固醇方法的适用性和有效性。通过用猪LDL免疫绵羊,并通过在LDL-琼脂糖凝胶上进行色谱法从其抗血清中选择性吸附抗体,来大规模生产和分离针对猪LDL(密度=1.006 - 1.063 g/ml)的单特异性抗体。然后将分离出的LDL抗体与琼脂糖凝胶CL-4B共价连接。抗LDL-琼脂糖凝胶珠在体外能有效去除猪血浆中的LDL。在猪身上进行了体内研究,(i)使用对分子量低于2,000,000的溶质可渗透的血浆分离膜,或(ii)在动静脉分流中插入血液离心机,以从血浆中分离出血液中的细胞成分。在这两种情况下,血浆都通过抗LDL-琼脂糖凝胶柱,并再循环到分流的静脉部分。通过该方法,血浆胆固醇水平降低了70 - 80%,且在体外免疫吸附程序后3 - 4天反弹。这种连续的血浆分离-免疫吸附程序可能对消除任何具有抗原特性的血浆成分具有广泛的适用性。