Uptake and catabolism of low density lipoprotein by human lymphocytes

Abstract

BROWN and Goldstein^1,2 have shown that when cultured human fibroblasts are incubated in the presence of low density lipoprotein (LDL), they take up some LDL, the apoprotein of LDL (apoLDL) is catabolised and cholesterol synthesis is inhibited. Experiments on the uptake of LDL as a function of LDL concentration have led to the conclusion^1,2 that normal fibroblasts have genetically controlled surface receptors with high affinity for apoLDL and that uptake of LDL by the receptors is essential for the regulation of cholesterol synthesis. These findings raise the possibility that receptor-mediated uptake by fibroblasts, and perhaps by other cells^3,4, has an important role in the regulation of apoLDL catabolism and of cholesterol synthesis in vivo. But the concentration of LDL protein required to saturate the LDL receptors on cultured fibroblasts (about 50 µg ml⁻¹) is less than half the probable concentration in interstitial fluid⁵. Moreover, whereas cultured fibroblasts from patients with familial hypercholesterolaemia (FH) in the homozygous form synthesise cholesterol at 50 times the normal rate, the rate of synthesis of cholesterol in the whole bodies of FH patients is usually normal⁶ or subnormal⁷. For these reasons it seemed desirable to study the binding and catabolism of LDL by uncultured human cells. We used circulating lymphocytes because they can be obtained readily and repeatedly from healthy human subjects. Our results show that uncultured lymphocytes exhibit high capacity surface binding of LDL, but the binding curves show no evidence for the presence of high affinity receptors for LDL.