Jauhiainen M, Metso J, Pahlman R, Blomqvist S, van Tol A, Ehnholm C
National Public Health Institute, Department of Biochemistry, Helsinki, Finland.
J Biol Chem. 1993 Feb 25;268(6):4032-6.
The effect of human plasma phospholipid transfer protein (PLTP) on the particle size distribution of human high density lipoprotein (HDL) was studied by incubating human HDL3 (particle diameter, 8.7 nm) together with PLTP in vitro. Incubation of HDL3 with highly purified preparations of PLTP, devoid of cholesterol ester transfer protein (CETP), induced a conversion of the homogenous population of HDL particles into two main populations of particles, one larger, particle diameter 10.9 nm, and one smaller, particle diameter 7.8 nm, than the original HDL3. These size changes were evident as analyzed by gradient gel electrophoresis and by high resolution gel filtration. The degree of the conversion was dependent on the amount of PLTP added to the incubation and on incubation time. An inhibitory monoclonal antibody (TP-1) directed against CETP had no effect on the HDL conversion. The PLTP used was purified to homogeneity from human plasma using ultracentrifugation and a combination of hydrophobic, cation-exchange, heparin-Sepharose-, anion-exchange, and gel filtration chromatographies. The monoclonal anti-CETP antibody (TP-1), which inhibits lipid transfer catalyzed by CETP, did not react with PLTP or inhibit its activity. The estimated molecular weight of PLTP is 75,000. The present study demonstrates that PLTP can act like the putative conversion factor and has the ability to convert HDL3 into populations of larger and smaller HDL particles. The mechanism(s) involved in this process and its physiological relevance remain to be established.
通过在体外将人高密度脂蛋白3（HDL3，颗粒直径8.7nm）与人血浆磷脂转运蛋白（PLTP）共同孵育，研究了PLTP对人高密度脂蛋白（HDL）颗粒大小分布的影响。将HDL3与不含胆固醇酯转运蛋白（CETP）的高度纯化的PLTP制剂一起孵育，导致HDL颗粒的均匀群体转化为两个主要的颗粒群体，一个较大，颗粒直径10.9nm，一个较小，颗粒直径7.8nm，均大于原始的HDL3。通过梯度凝胶电泳和高分辨率凝胶过滤分析，这些大小变化很明显。转化程度取决于孵育中添加的PLTP量和孵育时间。针对CETP的抑制性单克隆抗体（TP-1）对HDL转化没有影响。所用的PLTP通过超速离心以及疏水、阳离子交换、肝素-琼脂糖、阴离子交换和凝胶过滤色谱法的组合从人血浆中纯化至同质。抑制CETP催化的脂质转运的抗CETP单克隆抗体（TP-1）不与PLTP反应或抑制其活性。PLTP的估计分子量为75,000。本研究表明，PLTP可以像假定的转化因子一样起作用，并且有能力将HDL3转化为更大和更小的HDL颗粒群体。这一过程涉及的机制及其生理相关性仍有待确定。
