Roles of human plasma phospholipid transfer protein in high-density lipoprotein metabolism

Abstract

A simple method for the purification of phospholipid transfer protein (PLTP) from human plasma was developed. Molecular weight (78 KD), isoelectric points (4.3-5.1), and some basic characteristics of PLTP were obtained by using the purified PLTP. The PL transfer activity of PLTP was varied depending upon the types of donors and acceptors employed in the assay systems. The increase in cholesterol content of synthetic donor particles substantially reduced the transfer. The increases in apo-A-I or apo-A-II contents of synthetic lipid particle preparations enhanced the transfer, with apo-A-II exerting a greater effect than apo-A-I. However, the apoproteins added to lipoproteins did not yield significant effects. The PL transfer activity of PLTP was considerably higher than that of LTP, especially when synthetic lipid particles rather than natural lipoproteins were used as donor particles. Plasma PLTP and LTP were responsible for about 60 and 40%, respectively, of PL exchange between LDL and HDL. However, PLTP was largely responsible for the transfer when synthetic donor particles were used in the assay systems. The purified PLTP also exhibited an activity to promote the conversion of HDL$\sb2$ and HDL$\sb3$ to the larger particles. The release of apo-A-I from HDL by PLTP during the conversion was confirmed by several experiments. The inclusion of apo-A-I in the incubation mixtures of HDL$\sb3$/PLTP caused a limited inhibition of the conversion, only when the PLTP concentration was low. PLTP was primarily responsible for plasma HDL conversion, as evidenced by the inhibitory effect of anti-PLTP-IgG and by the enhancing effect of purified PLTP added into the plasma on the conversion. The addition of apo-A-I into the plasma completely prevented the conversion. This strong inhibitory effect of apo-A-I was unique in the plasma system. The inhibitory effect of apo-A-I on the conversion was reduced by the addition of the purified PLTP into the plasma. The PLTP-mediated conversion of plasma HDL was enhanced in the presence of LCAT, and also LDL and VLDL.