Low-density lipoprotein (LDL) and lymphocyte responses: direct suppression by native LDL and indirect inhibition from zinc chelation by contaminating EDTA

Jennifer A. Cuthbert, Peter E. Lipsky

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Low-density lipoproteins (LDL) have been shown to have a number of effects on the function of various cell types. To appreciate whether the in vitro effects of LDL have in vivo relevance, it is necessary to demonstrate that the biologic action described can be accounted for by native LDL and not by an alteration in the molecule or an addition to the preparation occurring during isolation. EDTA is frequently added to LDL during preparation to prevent oxidation. The effect of EDTA dialysis on LDL-mediated inhibition of lymphocyte responses was therefore examined. LDL alone did not inhibit mitogen-induced initial lymphocyte activation but rather suppressed lymphocyte DNA synthesis and subsequent proliferation in a transferrinreversible manner. LDL dialysed with EDTA also inhibited lymphocyte responsiveness but the inhibition was not reversed by transferrin. Further experiments demonstrated that after dialysis, EDTA in the LDL accounted for the change in its inhibitory effects. EDTA did not alter the lipoprotein but itself inhibited lymphocyte responses by chelating zinc necessary for DNA synthesis. These data indicate that LDL preparations may exhibit at least two separate effects on lymphocyte function. LDL is directly suppressive, while small amounts of contaminating EDTA can additionally be suppressive by chelating zinc. Thus, EDTA present in LDL preparations can alter their apparent biologic effects.

Original languageEnglish (US)
Pages (from-to)210-219
Number of pages10
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume876
Issue number2
DOIs
StatePublished - Apr 15 1986

Keywords

  • DNA synthesis
  • EDTA
  • LDL
  • Lymphocyte activation
  • Zinc

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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