TY - JOUR
T1 - Low-density lipoprotein (LDL) and lymphocyte responses
T2 - direct suppression by native LDL and indirect inhibition from zinc chelation by contaminating EDTA
AU - Cuthbert, Jennifer A.
AU - Lipsky, Peter E.
N1 - Funding Information:
The authors wish to thank Ms. Linda Sewell for expert technical assistance and Mrs. Renate Davis for her skillful preparation of the manuscript. This work was supported by NIH grant AI17653.
PY - 1986/4/15
Y1 - 1986/4/15
N2 - 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.
AB - 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.
KW - DNA synthesis
KW - EDTA
KW - LDL
KW - Lymphocyte activation
KW - Zinc
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U2 - 10.1016/0005-2760(86)90276-6
DO - 10.1016/0005-2760(86)90276-6
M3 - Article
C2 - 3082366
AN - SCOPUS:0022481775
SN - 0005-2760
VL - 876
SP - 210
EP - 219
JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
IS - 2
ER -