MOLECULAR AND MACROMOLECULAR SPECIFICITY OF HUMAN PLASMA PHOSPHOLIPIDTRANSFER PROTEIN

Phospholipid transfer protein (PLTP), also known as lipid transfer pro tein 2 (LTP-2), mediates a transfer of phospholipids between high-dens ity lipoproteins (HDL). The molecular and macromolecular specificities of recombinant human PLTP were studied using a fluorometric assay bas ed on the excimer fluorescence of pyrenyl lipids. To determine lipopro tein specificity of PLTP, donor very low density lipoproteins (VLDL), low-density lipoproteins (LDL), and HDL were labeled with 1-palmitoyl- 2-[10-(1-pyrenyl)decanoyl] phosphatidylcholine (PPyDPC) and incubated with unlabeled acceptor VLDL, LDL, and HDL in every pairwise combinati on. The highest rate of PPyDPC transfer mediated by PLTP occurred betw een donor HDL and acceptor HDL. Reassembled HDL (rHDL) consisting of 1 -palmitoyl-2-oleoylphosphatidylcholine, apolipoprotein A-I, and pyrene lipids (100:1:4) were used to demonstrate that PLTP transfers diacylg lyceride > phosphatidic acid > sphingomyelin > phosphatidylcholine (PC ) > phosphatidylglycerol > cerobroside > phosphatidylethanolamine. Thu s, PLTP transfers a variety of lipids with two carbon chains and a pol ar head group. Unsaturation of one PC acyl chain greatly increased tra nsfer rate, whereas increasing chain length and exchanging sn-1/sn-2 p osition had only small effects. The rate of PPyDPC transfer by PLTP de creases with increasing free cholesterol content in rHDL and with decr easing HDL size. In contrast to spontaneous transfer, PLTP mediates th e accumulation of PC in small rHDL particles. PLTP may be important in vivo in the recycling of PC from mature HDL to nascent HDL, the latte r of which are the initial accepters of cholesterol from peripheral ti ssue for reverse cholesterol transport to the liver.