Abstract
To study the mechanism of cholesterol deposition in the monocyte-macrophage (foam cell formation), we incubated peritoneal macrophages from normal and Watanabe heritable hyperlipidemic (WHHL) rabbits with various types of lipoprotein. Rabbit macrophages were induced by intraperitoneal injection of liquid paraffin oil. Each dish contained 2×106 adherent cell which had characteristics of macrophage. After 18 hours incubation with DMEM, mechanism of lipoprotein uptake was investigated by reacylation reaction of [14C]oleate with cholesterol and degradation of 125I-labeled lipoproteins. When incubated with normal rabbit macrophages for 5 hours, 50μg/ml of human LDL, acetyl LDL, and rabbit β-VLDL stimulated the cholesteryl [14C]oleate synthesis of 30, 15, and 35nmol/mg protein, respectively. On the other hand, macrophages from WHHL rabbit showed different response. About 0, 15, and 24nmol/mg protein of cholesteryl [14C]oleate was synthesized by WHHL macrophages. When 50μg/ml of 125I β-VLDL was incubated with macrophages from normal and WHHL rabbit for 5 hours, 125I β-VLDL was degraded by saturable high affinity mechanism. Each macrophage degraded 11.5 and 3.2μg/mg protein of 125I β-VLDL, respectively. This β-VLDL degradation was inhibited only by excess β-VLDL. These data suggest the existence of the receptor specific to β-VLDL. We have already reported that cholesterol rich very low density lipoprotein from WHHL rabbit stimulates cholesteryl ester synthesis in mouse peritoneal macrophages via β-VLDL receptor. Considered together, macrophages from WHHL rabbit may accumulate cholesteryl ester by taking up cholesterol rich VLDL via their β-VLDL receptor, and this mechanism may be responsible for atherogenesity of patients of homozygote FH.
