Metabolism of human plasma triacylglycerol-rich lipoproteins in rodent macrophages: capacity for interaction at β-VLDL receptor

Abstract

The capacity of human plasma triacylglycerol-rich lipoproteins to be metabolized by rat macrophages was studied with plasma triacylglycerol-rich lipoproteins obtained from subjects with fasting chylomicronemia or from normal subjects after a fat meal. Triacylglycerol-rich lipoproteins were separated by chromatography into two fractions designated TRL 1 and TRL 2; from their composition and changing concentration during alimentary lipemia, TRL 1 contained a higher proportion of chylomicron remnants than TRL 2. Degradation of 125I-labeled TRL 1 was greater than that of 125I-labeled TRL 2. In competition studies with 125I-labeled β-VLDL from cholesterol-fed rabbits, unlabeled TRL 1 displaced β-VLDL as completely as did unlabeled β-VLDL, being slightly more potent than TRL 2, which contained less apolipoprotein E than TRL 1. This reflected common interaction at receptors that probably included both β-VLDL and B/E receptors, since: (1) in fresh macrophages, VLDL from hypertriglyceridemic subjects partially displaced β-VLDL; (2) in B/E receptor-repressed macrophages, TRL 1 maintained capacity to totally displace β-VLDL. This was confirmed in experiments with J774 murine macrophages in which triacylglycerol-rich lipoproteins and β-VLDL displaced each other equally, whereas LDL was ineffective in displacing β-VLDL. Furthermore, monoclonal antibodies raised against apolipoprotein B 48 and reacting strongly with LDL, failed to inhibit the binding of triacylglycerol-rich lipoprotein to the macrophages. This indicates an interaction through apolipoprotein E which is present in high concentration in triacylglycerol-rich lipoprotein as well as in β-VLDL. It applies to triacylglycerol-rich particles derived from either the intestine (chylomicron remnants) or the liver (VLDL remnants from hypertriglyceridemic subjects).