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Journal of Lipid Research, Vol. 41, 376-383, March 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Interleukin-4 augments acetylated LDL-induced cholesterol esterification in macrophages

Correspondence to: Joseph A. Cornicelli

Correspondence to: Alan Daugherty

Activated subpopulations of lymphocytes and mast cells have been detected in atherosclerotic lesions. Interleukin-4 (IL-4) is a prominent cytokine released during activation of both cell types and its transcripts have been detected in both human and mouse atherosclerotic lesions. To define whether this local release of IL-4 influences macrophage lipid metabolism, we examined the effects of this cytokine on intracellular cholesterol esterification during incubation with modified low density lipoprotein (LDL). IL-4 greatly augmented cholesterol esterification induced by acetylated LDL (AcLDL) in both mouse peritoneal macrophages and the murine macrophage cell line, J774. This augmentation was maximal at a concentration of 1 ng/ml after incubation for 48 h. This was not a generalized effect on lipoprotein metabolism as IL-4 had no effect on cholesterol esterification in the presence of either LDL or ß-VLDL. Determination of binding isotherms demonstrated that IL-4 increased the number of cell surface binding sites for AcLDL. The IL-4-augmented AcLDL-induced cholesterol esterification was attenuated by the scavenger receptor class A (SR-A) antagonist, fucoidan, and the anti-mouse SR-A monoclonal antibody, 2F8.

These data, combined with the known receptor specificity of AcLDL interactions, imply a role of SR-A in the IL-4 induced responses. Two cytokines that have been demonstrated previously to down-regulate SR-A, TNF- and TGF-ß, antagonized the IL-4-induced augmentation of cholesterol esterification. Therefore, local release of IL-4 within atherosclerotic lesions could have a profound effect on macrophage lipid metabolism and the subsequent atherogenic process.—Cornicelli, J. A., D. Butteiger, D. L. Rateri, K. Welch, and A. Daugherty. Interleukin-4 augments acetylated LDL-induced cholesterol esterification in macrophages. J. Lipid Res. 2000. 41: 376;–383.

Supplementary key words: scavenger receptor, CD36, LDL, ß-VLDL, cytokines

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