Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins

J Clin Invest. 1999 Jan;103(1):117-28. doi: 10.1172/JCI4533.


We recently cloned monoclonal IgM autoantibodies which bind to epitopes of oxidized low-density lipoprotein (OxLDL) from apoE-deficient mice (EO- autoantibodies). We now demonstrate that those EO- autoantibodies that were originally selected for binding to copper-oxidized low-density lipoproteins (CuOx-LDL), also bound both to the oxidized protein and to the oxidized lipid moieties of CuOx-LDL. The same EO- autoantibodies showed specific binding to products of oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine (OxPAPC) and to the specific oxidized phospholipid, 1-palmitoyl-2-(5-oxovaleroyl)-phosphatidyl-choline (POVPC), whereas oxidation of fatty acids (linoleic or arachidonic acid) or cholesteryl esters (cholesteryl-oleate or cholesteryl-linoleate) did not yield any binding activity. Those EO- autoantibodies that bound to oxidized phospholipids (e.g., EO6) inhibited the binding and degradation of CuOx-LDL by mouse peritoneal macrophages up to 91%, whereas other IgM EO- autoantibodies, selected for binding to malondialdehyde (MDA)-LDL, had no influence on binding of either CuOx-LDL or MDA-LDL by macrophages. F(ab')2 fragments of EO6 were equally effective as the intact EO6 in preventing the binding of CuOx-LDL by macrophages. The molar ratios of IgM to LDL needed to maximally inhibit the binding varied from approximately 8 to 25 with different CuOx-LDL preparations. Finally, a POVPC-bovine serum albumin (BSA) adduct also inhibited CuOx-LDL uptake by macrophages. These data suggest that oxidized phospholipid epitopes, present either as lipids or as lipid-protein adducts, represent one class of ligands involved in the recognition of OxLDL by macrophages, and that apoE-deficient mice have IgM autoantibodies that can bind to these neoepitopes and inhibit OxLDL uptake.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Autoantibodies / immunology
  • Autoantibodies / metabolism
  • Copper / pharmacology
  • Emulsions / metabolism
  • Epitopes / immunology
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism
  • Lipid Peroxides / immunology
  • Lipoproteins, LDL / immunology*
  • Lipoproteins, LDL / metabolism
  • Liposomes / immunology
  • Liposomes / metabolism
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Phospholipids / immunology
  • Protein Binding


  • Antibodies, Monoclonal
  • Apolipoproteins E
  • Autoantibodies
  • Emulsions
  • Epitopes
  • Immunoglobulin Fab Fragments
  • Lipid Peroxides
  • Lipoproteins, LDL
  • Liposomes
  • Phospholipids
  • oxidized low density lipoprotein
  • Copper