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J. Lipid Res.
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A more recent version of this article appeared on July 1, 2004

Papers In Press, published online ahead of print April 21, 2004
J. Lipid Res., doi:10.1194/jlr.M400075-JLR200
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Submitted on February 22, 2004
Revised on April 1, 2004
Accepted on April 5, 2004

Autoantibodies to OxLDL fail to alter 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

Department of Pathology, University of Chicago, Chicago, IL 60637-1470

Corresponding Author: getz{at}delphi.bsd.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 was injected into immune competent apoE-/- mice and immune deficient apoE-/-RAG2-/- 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 E06 antibody on the human LDL increased over time suggesting de novo oxidation of the LDL or transfer of OxPL to the particles. Since the native LDL was not extensively modified, we also examined the clearance of copper oxidized LDL. While the extensively oxidized LDL was cleared faster than the native LDL, there was no difference in the rate of clearance as a function of immune status. There appears to be some transfer of OxPL to the endogenous murine LDL in the immune deficient mice. 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.


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