Low density lipoprotein degradation by mononuclear cells from normal and dyslipoproteinemic subjects

Three major characteristics of cell surface low density lipoprotein (LDL) receptor activity in fibroblasts or lymphocytes are high-affinity LDL binding or degradation, specificity for LDL, and "inducibility"--that is, the ability to increase when cells are cultured in the absence of lipoproteins. Cells from patients with receptor-negative homozygous familial hypercholesterolemia (FH) have been reported to express none of these characteristics, and the patients are thought to have a genetic absence of LDL receptors. We found that, although induced receptor-negative lymphocytes degraded less LDL than did normal lymphocytes, the curves for LDL degradation versus LDL concentration were biphasic, with greater concentration-dependence at LDL concentrations less than 60 micrograms/ml, indicating high-affinity LDL degradation. The percentage of specific LDL degradation by induced receptor-negative lymphocytes was two-thirds of normal with LDL at 10 micrograms/ml and increased to normal at 50 micrograms/ml, an LDL concentration still within the range of high-affinity degradation. Receptor-negative lymphocytes could be induced by incubation in the absence of lipoproteins to degrade twice as much LDL as they did when freshly isolated. Freshly isolated cells from abetalipoproteinemic patients and one receptor-negative patient degraded as much LDL as did fresh normal cells. The findings indicate that receptor-negative lymphocytes have a mechanism for facilitated uptake of LDL that resembles that of normal lymphocytes, although it is not as efficient.