Literature DB >> 6087331

Modulation of human lymphocyte responses by low density lipoproteins (LDL): enhancement but not immunosuppression is mediated by LDL receptors.

J A Cuthbert, P E Lipsky.   

Abstract

The role of low density lipoprotein (LDL) receptors in mediating the immunomodulatory effects of LDL was examined by comparing responses of normal lymphocytes with those obtained from a patient with familial hypercholesterolemia (FH) lacking receptors for LDL. The function of LDL receptors in supporting lymphocyte growth was demonstrated by blocking endogenous sterol synthesis with mevinolin, a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and culturing cells in lipoprotein-deficient medium with supplemental LDL as the only source of cholesterol. Mevinolin inhibited mitogen-induced proliferation of normal and FH lymphocytes. Whereas inhibition was overcome by mevalonate, the product of the inhibited enzyme, low concentrations of LDL (less than 10 micrograms of protein/ml) restored the responses of normal but not FH lymphocytes. When normal and FH lymphocytes were cultured in the absence of mevinolin, high concentrations of LDL (greater than 100 micrograms of protein/ml) inhibited mitogen-induced lymphocyte proliferation. The inhibitory effects on normal and FH lymphocytes were similar in that both required comparably large concentrations of LDL and could be completely reversed by transferrin. When normal lymphocytes were cultured in serum-free medium supplemented with transferrin, low concentrations of LDL (less than 10 micrograms of protein/ml) caused marked augmentation of proliferation. By contrast, no enhancement of FH lymphocyte growth was observed. These results indicate that LDL-mediated enhancement of lymphocyte growth in the presence or absence of endogenous sterol biosynthesis involves specific receptors for LDL whereas the immunosuppression caused by LDL is independent of these receptors. Moreover, the results suggest that peripheral lymphocytes can be used to evaluate the functional integrity of the receptor-mediated uptake of LDL.

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Year:  1984        PMID: 6087331      PMCID: PMC345626          DOI: 10.1073/pnas.81.14.4539

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  19 in total

1.  Inhibition of cholesterol synthesis with compactin renders growth of cultured cells dependent on the low density lipoprotein receptor.

Authors:  J L Goldstein; J A Helgeson; M S Brown
Journal:  J Biol Chem       Date:  1979-06-25       Impact factor: 5.157

Review 2.  The low-density lipoprotein pathway and its relation to atherosclerosis.

Authors:  J L Goldstein; M S Brown
Journal:  Annu Rev Biochem       Date:  1977       Impact factor: 23.643

3.  Genetics of the low density lipoprotein receptor. Diminished receptor activity in lymphocytes from heterozygotes with familial hypercholesterolemia.

Authors:  D W Bilheimer; Y K Ho; M S Brown; R G Anderson; J L Goldstein
Journal:  J Clin Invest       Date:  1978-03       Impact factor: 14.808

4.  Biologically active low density lipoprotein in human peripheral lymph.

Authors:  D Reichl; N B Myant; M S Brown; J L Goldstein
Journal:  J Clin Invest       Date:  1978-01       Impact factor: 14.808

5.  Inhibition of lymphocyte proliferation stimulated by lectins and allogeneic cells by normal plasma lipoproteins.

Authors:  J H Morse; L D Witte; D S Goodman
Journal:  J Exp Med       Date:  1977-12-01       Impact factor: 14.307

6.  Relation of cholesterol and mevalonic acid to the cell cycle in smooth muscle and swiss 3T3 cells stimulated to divide by platelet-derived growth factor.

Authors:  A J Habenicht; J A Glomset; R Ross
Journal:  J Biol Chem       Date:  1980-06-10       Impact factor: 5.157

Review 7.  The LDL receptor locus and the genetics of familial hypercholesterolemia.

Authors:  J L Goldstein; M S Brown
Journal:  Annu Rev Genet       Date:  1979       Impact factor: 16.830

8.  Immunoregulation by low density lipoproteins in man. Inhibition of mitogen-induced T lymphocyte proliferation by interference with transferrin metabolism.

Authors:  J A Cuthbert; P E Lipsky
Journal:  J Clin Invest       Date:  1984-04       Impact factor: 14.808

9.  Sterol metabolism and lymphocyte function: inhibition of endogenous sterol biosynthesis does not prevent mitogen-induced human T lymphocyte activation.

Authors:  J A Cuthbert; P E Lipsky
Journal:  J Immunol       Date:  1980-05       Impact factor: 5.422

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

Authors:  Y K Ho; S Brown; D W Bilheimer; J L Goldstein
Journal:  J Clin Invest       Date:  1976-12       Impact factor: 14.808

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  6 in total

1.  mRNA for low density lipoprotein receptor in brain and spinal cord of immature and mature rabbits.

Authors:  S L Hofmann; D W Russell; J L Goldstein; M S Brown
Journal:  Proc Natl Acad Sci U S A       Date:  1987-09       Impact factor: 11.205

2.  Increased proliferative response of lymphocytes from intestinal lymph during long chain fatty acid absorption.

Authors:  S Miura; H Imaeda; H Shiozaki; N Ohkubo; H Tashiro; H Serizawa; M Tsuchiya; P Tso
Journal:  Immunology       Date:  1993-01       Impact factor: 7.397

3.  Apolipoprotein E localization in human coronary atherosclerotic plaques by in situ hybridization and immunohistochemistry and comparison with lipoprotein lipase.

Authors:  K D O'Brien; S S Deeb; M Ferguson; T O McDonald; M D Allen; C E Alpers; A Chait
Journal:  Am J Pathol       Date:  1994-03       Impact factor: 4.307

4.  Effects of lovastatin on natural killer cell function and other immunological parameters in man.

Authors:  R McPherson; C Tsoukas; M G Baines; A Vost; M R Melino; R V Zupkis; H F Pross
Journal:  J Clin Immunol       Date:  1993-11       Impact factor: 8.317

5.  Cholesterol lowering modulates T cell function in vivo and in vitro.

Authors:  Kuang-Yuh Chyu; Wai Man Lio; Paul C Dimayuga; Jianchang Zhou; Xiaoning Zhao; Juliana Yano; Portia Trinidad; Tomoyuki Honjo; Bojan Cercek; Prediman K Shah
Journal:  PLoS One       Date:  2014-03-19       Impact factor: 3.240

6.  A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

Authors:  Valentijn Vergote; Lies Laenen; Bert Vanmechelen; Marc Van Ranst; Erik Verbeken; Jay W Hooper; Piet Maes
Journal:  PLoS Negl Trop Dis       Date:  2017-10-27
  6 in total

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