Intracellular trafficking of pigeon beta-very low density lipoprotein and low density lipoprotein at low and high concentrations in pigeon macrophages

Foam cell formation occurs in vitro at lipoprotein concentrations above 50 mug/ml in pigeon macrophages, Hypothetically, intracellular trafficking of lipoproteins at higher concentrations may differ from uptake of lipoprotein s associated with low concentrations, revealing a separate atherogenic endo cytic pathway. Macrophage intracellular trafficking of pigeon beta -very lo w density lipoprotein (beta -VLDL) and low density lipoprotein (LDL) at low concentrations (12 mug/ml) near the saturation of high affinity binding si tes and high lipoprotein concentrations (50-150 mug/ml) used to induce foam cell formation were examined. Pigeon beta -VLDL and LDL, differentially la beled with colloidal gold, were added simultaneously to contrast traffickin g of beta -VLDL, which causes in vitro foam cell formation, with LDL, which does not. The binding of lipoproteins to cell surface structures, distribu tion of lipoproteins in endocytic organelles, and the extent of colabeling in the endocytic organelles were determined by thin-section transmission el ectron microscopy. At low concentrations, the intracellular trafficking of pigeon LDL and beta -VLDL was identical. At high concentrations, LDL was re moved more rapidly from the plasma membrane and reached lysosomes more quic kly than beta -VLDL. No separate endocytic route was present at high concen trations of beta -VLDL; rather, an increased residence on the plasma membra ne, association with nonmicrovillar portions of the plasma membrane, and sl ower trafficking in organelles of coated-pit endocytosis reflected a more a therogenic trafficking pattern.