Immunoregulation by low density lipoproteins in man: Low density lipoprotein inhibits mitogen-stimulated human lymphocyte proliferation after initial activation

J. A. Cuthbert, P. E. Lipsky

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Low density lipoprotein (LDL, d 1.020-1.050 g/ml), isolated from normal human plasma by ultracentrifugation, inhibited mitogen-stimulated proliferation of human lymphocytes in a concentration-dependent manner. In order to characterize the inhibition more fully, the effect of LDL on initial lymphocyte activation and subsequent DNA synthesis was investigated. LDL had no effect on lymphocyte blast transformation assessed by quantitating the change in volume of the stimulated cells after a 24-hour incubation. Moreover, initial lymphocyte activation assessed by mitogen-stimulated RNA or protein synthesis was not inhibited by LDL. Finally, the acquisition of transferrin or T cell growth factor receptors by the activated lymphocytes was not affected by LDL, DNA synthesis, evaluated by measuring the incorporation of [3H]thymidine between 30 and 48 hours of culture was inhibited by LD in a concentration-dependent manner. The DNA content of individual mitogen-stimulated cells was analyzed by flow cytometry after mithramycin staining. These studies confirmed that LDL inhibited DNA synthesis in the initially activated lymphocytes. In addition, LDL in concentrations that did not inhibit initial DNA synthesis did suppress cell division and lymphocyte proliferation. These results indicate that LDL inhibits lymphocyte responses by exerting inhibitory effects on DNA synthesis, cell division, and subsequent growth of the activated cells rather than by altering initial lymphocyte blast transformation. LDL thus may play a role in regulating clonal expansion of activated lymphocytes during immune response.

Original languageEnglish (US)
Pages (from-to)1512-1524
Number of pages13
JournalJournal of Lipid Research
Volume24
Issue number11
StatePublished - 1983

Fingerprint

Lymphocytes
Mitogens
LDL Lipoproteins
Lymphocyte Activation
Chemical activation
DNA
Cell Division
Plicamycin
Cells
oxidized low density lipoprotein
Interleukin-2 Receptors
Ultracentrifugation
Plasma (human)
Transferrin
Cell Size
Thymidine
Flow cytometry
Flow Cytometry
RNA
Staining and Labeling

ASJC Scopus subject areas

  • Endocrinology

Cite this

@article{43ac2ad888ff438fb724d210d8471868,
title = "Immunoregulation by low density lipoproteins in man: Low density lipoprotein inhibits mitogen-stimulated human lymphocyte proliferation after initial activation",
abstract = "Low density lipoprotein (LDL, d 1.020-1.050 g/ml), isolated from normal human plasma by ultracentrifugation, inhibited mitogen-stimulated proliferation of human lymphocytes in a concentration-dependent manner. In order to characterize the inhibition more fully, the effect of LDL on initial lymphocyte activation and subsequent DNA synthesis was investigated. LDL had no effect on lymphocyte blast transformation assessed by quantitating the change in volume of the stimulated cells after a 24-hour incubation. Moreover, initial lymphocyte activation assessed by mitogen-stimulated RNA or protein synthesis was not inhibited by LDL. Finally, the acquisition of transferrin or T cell growth factor receptors by the activated lymphocytes was not affected by LDL, DNA synthesis, evaluated by measuring the incorporation of [3H]thymidine between 30 and 48 hours of culture was inhibited by LD in a concentration-dependent manner. The DNA content of individual mitogen-stimulated cells was analyzed by flow cytometry after mithramycin staining. These studies confirmed that LDL inhibited DNA synthesis in the initially activated lymphocytes. In addition, LDL in concentrations that did not inhibit initial DNA synthesis did suppress cell division and lymphocyte proliferation. These results indicate that LDL inhibits lymphocyte responses by exerting inhibitory effects on DNA synthesis, cell division, and subsequent growth of the activated cells rather than by altering initial lymphocyte blast transformation. LDL thus may play a role in regulating clonal expansion of activated lymphocytes during immune response.",
author = "Cuthbert, {J. A.} and Lipsky, {P. E.}",
year = "1983",
language = "English (US)",
volume = "24",
pages = "1512--1524",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "11",

}

TY - JOUR

T1 - Immunoregulation by low density lipoproteins in man

T2 - Low density lipoprotein inhibits mitogen-stimulated human lymphocyte proliferation after initial activation

AU - Cuthbert, J. A.

AU - Lipsky, P. E.

PY - 1983

Y1 - 1983

N2 - Low density lipoprotein (LDL, d 1.020-1.050 g/ml), isolated from normal human plasma by ultracentrifugation, inhibited mitogen-stimulated proliferation of human lymphocytes in a concentration-dependent manner. In order to characterize the inhibition more fully, the effect of LDL on initial lymphocyte activation and subsequent DNA synthesis was investigated. LDL had no effect on lymphocyte blast transformation assessed by quantitating the change in volume of the stimulated cells after a 24-hour incubation. Moreover, initial lymphocyte activation assessed by mitogen-stimulated RNA or protein synthesis was not inhibited by LDL. Finally, the acquisition of transferrin or T cell growth factor receptors by the activated lymphocytes was not affected by LDL, DNA synthesis, evaluated by measuring the incorporation of [3H]thymidine between 30 and 48 hours of culture was inhibited by LD in a concentration-dependent manner. The DNA content of individual mitogen-stimulated cells was analyzed by flow cytometry after mithramycin staining. These studies confirmed that LDL inhibited DNA synthesis in the initially activated lymphocytes. In addition, LDL in concentrations that did not inhibit initial DNA synthesis did suppress cell division and lymphocyte proliferation. These results indicate that LDL inhibits lymphocyte responses by exerting inhibitory effects on DNA synthesis, cell division, and subsequent growth of the activated cells rather than by altering initial lymphocyte blast transformation. LDL thus may play a role in regulating clonal expansion of activated lymphocytes during immune response.

AB - Low density lipoprotein (LDL, d 1.020-1.050 g/ml), isolated from normal human plasma by ultracentrifugation, inhibited mitogen-stimulated proliferation of human lymphocytes in a concentration-dependent manner. In order to characterize the inhibition more fully, the effect of LDL on initial lymphocyte activation and subsequent DNA synthesis was investigated. LDL had no effect on lymphocyte blast transformation assessed by quantitating the change in volume of the stimulated cells after a 24-hour incubation. Moreover, initial lymphocyte activation assessed by mitogen-stimulated RNA or protein synthesis was not inhibited by LDL. Finally, the acquisition of transferrin or T cell growth factor receptors by the activated lymphocytes was not affected by LDL, DNA synthesis, evaluated by measuring the incorporation of [3H]thymidine between 30 and 48 hours of culture was inhibited by LD in a concentration-dependent manner. The DNA content of individual mitogen-stimulated cells was analyzed by flow cytometry after mithramycin staining. These studies confirmed that LDL inhibited DNA synthesis in the initially activated lymphocytes. In addition, LDL in concentrations that did not inhibit initial DNA synthesis did suppress cell division and lymphocyte proliferation. These results indicate that LDL inhibits lymphocyte responses by exerting inhibitory effects on DNA synthesis, cell division, and subsequent growth of the activated cells rather than by altering initial lymphocyte blast transformation. LDL thus may play a role in regulating clonal expansion of activated lymphocytes during immune response.

UR - http://www.scopus.com/inward/record.url?scp=0021088349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021088349&partnerID=8YFLogxK

M3 - Article

C2 - 6197501

AN - SCOPUS:0021088349

VL - 24

SP - 1512

EP - 1524

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 11

ER -