Abstract
Foam cell formation occurs in vitro at lipoprotein concentrations above 50 μg/ml in pigeon macrophages. Hypothetically, intracellular trafficking of lipoproteins at higher concentrations may differ from uptake of lipoproteins associated with low concentrations, revealing a separate atherogenic endocytic pathway. Macrophage intracellular trafficking of pigeon β-very low density lipoprotein (β-VLDL) and low density lipoprotein (LDL) at low concentrations (12 μg/ml) near the saturation of high affinity binding sites and high lipoprotein concentrations (50–150 μg/ml) used to induce foam cell formation were examined. Pigeon β-VLDL and LDL, differentially labeled with colloidal gold, were added simultaneously to contrast trafficking of β-VLDL, which causes in vitro foam cell formation, with LDL, which does not. The binding of lipoproteins to cell surface structures, distribution of lipoproteins in endocytic organelles, and the extent of colabeling in the endocytic organelles were determined by thin-section transmission electron microscopy. At low concentrations, the intracellular trafficking of pigeon LDL and β-VLDL was identical. At high concentrations, LDL was removed more rapidly from the plasma membrane and reached lysosomes more quickly than β-VLDL. No separate endocytic route was present at high concentrations of β-VLDL; rather, an increased residence on the plasma membrane, association with nonmicrovillar portions of the plasma membrane, and slower trafficking in organelles of coated-pit endocytosis reflected a more atherogenic trafficking pattern.—Jones, N. L., J. A. Saunders, and R. R. Mallory. Intracellular trafficking of pigeon β-very low density lipoprotein and low density lipoprotein at low and high concentrations in pigeon macrophages. J. Lipid Res. 2000. 41: 1823–1831.
Highlights
Foam cell formation occurs in vitro at lipoprotein concentrations above 50 g/ml in pigeon macrophages
Previous studies speculated that intracellular processing of lipoproteins that stimulate cholesteryl ester accumulation and subsequent foam cell formation is different from the processing of those lipoproteins that do not cause foam cell formation [5]
The time course of endocytosis at low concentration (12 g/ml) of --very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in macrophages was similar to endocytosis of LDL alone. -VLDL and LDL maximally entered the clathrin-coated pits and vesicular profiles and early endosomes by 5 min, spherical endosomes by 10 min, late endosomal-prelysosomal tubuloreticular compartments (LEPT) by 60 min, and lysosomes by 2 h (Fig. 1)
Summary
Foam cell formation occurs in vitro at lipoprotein concentrations above 50 g/ml in pigeon macrophages. Previous studies speculated that intracellular processing of lipoproteins that stimulate cholesteryl ester accumulation and subsequent foam cell formation is different from the processing of those lipoproteins that do not cause foam cell formation [5] This is the case for the modified LDLs, AcLDL and OxLDL. To date ultrastructural studies have examined lipoproteins only at concentrations near the saturation of the high affinity binding sites rather than examining if a separate atherogenic endocytic route is present at concentrations used to induce foam cell formation. Another hypothesis for atherogenic trafficking of lipoproteins is delayed trafficking to lysosomes, rather than a separate endocytic pathway. Like human macrophages [1] they can be stimulated by endocytosis of either -very low density lipoprotein (-VLDL), acetylated low Abbreviations: ACAT, acyl-coenzyme A:cholesterol acyltransferase; AcLDL, acetylated LDL; apo, apolipoprotein; -VLDL, -very low density lipoprotein; HDL, high density lipoprotein; HSPG, heparan sulfate proteoglycan; LDL, low density lipoprotein; LEPT, late endosomalprelysosomal tubular compartment; OxLDL, oxidized LDL; PBS, phosphate-buffered saline; TEM, transmission electron microscopy; STEM, surface tubules for entry into macrophages
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