Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes

Y. K. Ho, M. S. Brown, D. W. Bilheimer, J. L. Goldstein

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Abstract

Circulating human lymphocytes freshly isolated from venous blood of 15 normal subjects exhibited a low capacity to bind, take up, and degrade 125I labeled low density lipoprotein (LDL). However, when these cells were incubated for 72 h in the absence of lipoproteins, they gradually acquired an increased number of high affinity cell surface receptors for LDL. The increase in the number of LDL receptors was associated with a 16 fold increase in the rate at which the cells were able to take up and degrade the lipoprotein. The LDL binding and degradation processes that developed in normal lymphocytes exhibited the following characteristics: high affinity (saturation was achieved at LDL concentrations below 50 μg protein/ml); specificity (unlabeled LDL was much more effective than human high density lipoprotein or other plasma proteins in competing with 125I LDL for binding to the LDL receptor); and feedback regulation (the increase in the number of LDL receptors that appeared after incubation of freshly isolated lymphocytes in lipoprotein deficient medium was prevented by exposure of the cells to either LDL or a mixture of 25 hydroxycholesterol plus cholesterol but not to HDL). Freshly isolated lymphocytes obtained from three subjects with the homozygous form of familial hypercholesterolemia failed to develop normal amounts of LDL receptor activity when incubated in medium devoid of lipoproteins. The current data indicate: that the LDL receptors that appear on the surface of cholesterol deprived, normal human lymphocytes are genetically identical to the previously characterized LDL receptors of cultured human fibroblasts and long term lymphoid cells and that at least one cell type in the human body, the circulating human lymphocyte, has the capacity to produce a high affinity LDL receptor that mediates the cellular uptake and degradation of plasma LDL.

Original languageEnglish (US)
Pages (from-to)1465-1474
Number of pages10
JournalJournal of Clinical Investigation
Volume58
Issue number6
DOIs
StatePublished - 1976

ASJC Scopus subject areas

  • Medicine(all)

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