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Journal of Lipid Research, Vol. 45, 1347-1354, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Autoantibodies to OxLDL fail to alter the clearance of injected OxLDL in apolipoprotein E-deficient mice

Catherine A. Reardon^*, Elizabeth R. Miller, Lydia Blachowicz^*, John Lukens^*, Christoph J. Binder, Joseph L. Witztum and Godfrey S. Getz^1,*

^* Department of Pathology, University of Chicago, Chicago, IL 60637
Department of Medicine, University of California, San Diego, CA 92093

¹ To whom correspondence should be addressed. e-mail: g-getz{at}uchicago.edu

This study tests the hypothesis that autoantibodies to oxidation epitopes on oxidized LDL (OxLDL) promote the clearance of OxLDL from the plasma. Human LDL (hLDL) was injected into immune-competent apolipoprotein E-deficient (apoE^–/–) mice and immune-deficient apoE^–/–/recombination-activating gene-deficient mice that lack mature T and B cells and thus antibodies. There was a progressive decrease in human apoB-100 in the plasma in all mice, but the rate of clearance was not greater in the immune-competent mice than in the immune-deficient mice. Interestingly, oxidized phospholipid (OxPL) epitopes as detected by the EO6 antibody on the hLDL increased over time, suggesting de novo oxidation of the LDL or transfer of OxPL to the particles. Because the native LDL was not extensively modified, we also examined the clearance of copper OxLDL. Although the extensively OxLDL was cleared faster than the native LDL, there was no difference in the rate of clearance as a function of immune status. There appeared to be some transfer of OxPL to the endogenous murine LDL.

Together, these results suggest that oxidation-specific antibodies do not participate to any great extent in the clearance of OxLDL from plasma. However, it is possible that such antibodies may bind to oxidation epitopes and modulate lesion formation within the vessel wall.

Abbreviations: apoE, apolipoprotein E; hLDL, human LDL; MDA-LDL, malondialdehyde-modified LDL; OxLDL, oxidized LDL; OxPL, oxidized phospholipid; PC, phosphorylcholine; RAG, recombination-activating gene 2; RLU, relative light units

Supplementary key words recombination-activating gene deficient • oxidized phospholipid • oxidized low density lipoprotein • human low density lipoprotein • EO6 antibodies

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