Preferential metabolism by macrophages of conditioned rabbit hypercholesterolemic remnant lipoproteins

Rabbits were fed a diet containing 1% cholesterol, and lipoproteins were isolated from their plasma by sequential ultracentrifugation. Lipoprotein remnants (d = 1.019-1.063) were conditioned by incubation with bovine aortic smooth muscle cells for 24 h and then incubated for 4 h with J774 cells or mouse peritoneal macrophages. Conditioning of remnants and low-density lipoproteins resulted in enhancement of their uptake and metabolism by the macrophages in culture. The macrophages metabolized conditioned remnant lipoproteins more extensively than controls at all concentrations tested. Addition of 10% safflower oil or 10% butter to the 1% cholesterol diet resulted in a molar ratio of linoleic/oleic acid of 1.62 and 0.62 in plasma neutral lipids and of 5.7 and 2.5 in plasma phospholipids. Conditioned remnants, derived after safflower oil feeding, were metabolized more extensively by macrophages than those obtained after butter feeding. This was also true for control remnants (preincubated without cells). Thiobarbituric acid-reactive substances were higher in remnants from safflower oil-fed than butter-fed rabbit plasma prior to and after conditioning. Mouse peritoneal macrophages metabolized remnant lipoproteins more extensively than low-density lipoproteins. The present results indicate that modification of remnant lipoproteins, the major atherogenic fraction of cholesterol-fed rabbit plasma, results in their enhanced metabolism by macrophages, and that an increase in the linoleic/oleic acid ratio in these lipoproteins might enhance their susceptibility to peroxidative modification.