[HTML][HTML] Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid–protein adducts inhibit macrophage uptake of oxidized low-density …

S Hörkkö, DA Bird, E Miller, H Itabe… - The Journal of …, 1999 - Am Soc Clin Investig
S Hörkkö, DA Bird, E Miller, H Itabe, N Leitinger, G Subbanagounder, JA Berliner…
The Journal of clinical investigation, 1999Am Soc Clin Investig
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 …
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 ∼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.
The Journal of Clinical Investigation