Acute effects of oxidized low density lipoprotein on metabolic responses in macrophages

Helga E. De Vries*, Eric Ronken, Jan Hendrik Reinders, Bas Buchner, Theo J.C. Van Berkel, Johan Kuiper

*Corresponding author for this work

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The immediate effects of oxidized low density lipoprotein (OxLDL) on the metabolic activity of cultured macrophages (RAW 264.7) were studied using a microphysiometer. Administration of OxLDL acutely induced a concentration- dependent increase in metabolic activity, with an EC50 of 16 ±3 μg/ml OxLDL and a maximal effect of 35% ± 4% (mean ± SEM; n=5). A biphasic response was measured after administration of 75 or 100 μg/ml OxLDL consisting of an initial sharp increase, followed by the induction of a long- lasting hypoactivity of 80% of the control value. Incubation of cells with polyinosinic acid (polyI; 100 μg/ml) for 30 min prior to OxLDL administration could completely block the effect of 25 μg/ml OxLDL. In addition, polyI acted as a full antagonist on the decrease of the biphasic response of cells generated by 75 and 100 μg/ml OxLDL. Macrophages used in this study possessed a specific binding site for OxLDL, with a dissociation constant (K(D)) of 9 ± 2 μg/ml and a maximal binding of 610 ± 32 ng 125I-OxLDL/mg cell protein. Binding of 125I-OxLDL to macrophages could be completely competed for by unlabeled OxLDL, by polyI for 58%, and by AcLDL for 46%. In conclusion, OxLDL can acutely activate the metabolic state of macrophages by a receptor-mediated process in a concentration-dependent fashion, which could be antagonized by polyI. Metabolic responses to OxLDL may underlie the changes observed in macrophages in the early atherosclerotic plaque.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalFASEB Journal
Issue number1
Publication statusPublished - 1998

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