Impaired capacity of acute-phase high density lipoprotein particles to deliver cholesteryl ester to the human HUH-7 hepatoma cell line

The major role of native high density Lipoprotein (HDL) is to carry cholesterol from peripheral tissues to the liver for bile excretion. As acute-phase (AP)-HDL has a decreased ability for cellular cholesterol efflux but an increased capacity for cholesteryl ester (CE) delivery to peripheral tissues, the interaction of AP-HDL with human hepatoma. cells was studied. Binding studies to HUH-7 cells revealed saturable binding properties for HDL and AP-HDL at 4degreesC. At 37degreesC, specific cell-association of I-125- and [1,2,6,7-H-3]-cholesteryl palmitate ([H-3]CE)-labeled lipoprotein particles was 2.2- and 1.6-fold higher for HDL indicating that total CE delivery was significantly (P < 0.05) higher for HDL in comparison to AP-HDL. In parallel, selective CE uptake (the difference between total lipid uptake and holoparticle uptake) from AP-HDL was decreased compared with HDL. The fact that the capacity for cellular cholesterol efflux from HUH-7 cells is slightly impaired by AP-HDL (compared with HDL) is of support that scavenger receptor class 13, type 1 (SR-BI), the only receptor so far known to mediate bi-directional lipid flux, might be involved in altered HUH-7 cholesterol hemostasis by AP-HDL. Our in vitro findings suggest that HDL and AP-HDL interact differently with cells of hepatic origin resulting in decreased hepatic cholesterol removal from the circulation during the AP reaction. (C) 2002 Else-vier Science Ltd. All rights reserved.