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

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Abstract
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, i.e., the ability to increase when cells are cultured in the absence of lipoproteins. Cells from patients with receptor-negative homozygous familial hypercholesterolemia (FH) were reported to express none of these characteristics, and the patients are thought to have a genetic absence of LDL receptors. Although induced receptor-negative lymphocytes degraded less LDL than did normal lymphocytes, the curves for LDL degradation vs. LDL concentration were biphasic, with greater concentration-dependence at LDL concentrations < 60 .mu.g/ml, indicating high-affinity LDL degradation. The percentage of specific LDL degradation by induced receptor-negative lymphocytes was 2/3 of normal with LDL at 10 .mu.g/ml and increased to normal at 50 .mu.g/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 1 receptor-negative patient degraded as much LDL as did fresh normal cells. Evidently, receptor-negative lymphocytes have a mechanism for facilitated uptake of LDL that resembles that of normal lymphocytes, although it is not as efficient.