Lipoprotein metabolism by macrophages from atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons

Abstract

The presence of specific receptors for the metabolism of acetylated low density lipoprotein (AcLDL) and beta-migrating very low density lipoprotein (beta-VLDL) was demonstrated in thioglycolate-elicited peritoneal macrophages from both atherosclerosis-susceptible White Carneau (WC) and resistant Show Racer (SR) pigeons. Macrophages from both breeds metabolized AcLDL through a single class of receptors that were similar, but not identical, to the scavenger receptors described in mammalian macrophages. Both pigeon and mammalian AcLDL bound to this receptor. At 37 degrees C, AcLDL was internalized and degraded in the lysosomes, and cholesterol esterification and cholesteryl ester accumulation were stimulated. As in mammalian macrophages, AcLDL receptor activity was not down-regulated by cholesterol loading. In contrast, AcLDL binding was poorly competed for by fucoidin or polyinosinic acid, and the magnitude of cholesteryl ester accumulation was only about one-half of that seen with mouse peritoneal macrophages. Pigeon beta-VLDL bound to both a high and a low affinity site on pigeon macrophages. Binding to the high affinity site was calcium-dependent, pronase-sensitive, and down-regulated by cholesterol loading. Cholesterol esterification and cholesteryl ester accumulation with beta-VLDL were stimulated to an equal or greater extent than with AcLDL. Unlike mammalian macrophages, the pigeon beta-VLDL receptor did not require apolipoprotein E, as evidenced by the lack of apoE in pigeon lipoproteins and by the failure of rabbit beta-VLDL, containing apoE, to compete for binding. Pigeon LDL, but not mammalian LDL, was recognized by the pigeon beta-VLDL receptor, suggesting that like the mammalian beta-VLDL receptor, the pigeon beta-VLDL receptor may be a form of an LDL receptor. This was an unexpected finding since pigeon fibroblasts and smooth muscle cells in culture do not express LDL receptors. Thus, pigeon macrophages have receptors for the uptake of abnormal lipoproteins that could play a role in the development of macrophage-derived foam cells that are prevalent in the early stages of atherosclerosis in this species. No quantitative or qualitative differences in these receptors, however, were identified that could account for the differences in atherosclerosis susceptibility between the WC and SR breeds.