Human-Derived Anti-Oxidized LDL Autoantibody Blocks Uptake of Oxidized LDL by Macrophages and Localizes to Atherosclerotic Lesions In Vivo

• DOI: 10.1161/hq0801.093587
• Publication Date: 2007-09-28T18:27:24Z
• Authors: Peter X. Shaw; Sohvi Hörkkö; Sotirios Tsimikas; Mi-Kyung Chang; Wulf Palinski; Gregg J. Silverman; Pojen P. Chen; Joseph L. Witztum
• Keywords: Foam cell; Low-density lipoprotein

Autoantibodies to oxidation-specific epitopes of low density lipoprotein (LDL), such as malondialdehyde-modified LDL (MDA-LDL), occur in plasma and atherosclerotic lesions humans animals. Plasma titers antibodies are correlated with atherosclerosis murine models, several autoantibodies have been cloned. However, human-derived monoclonal oxidized (OxLDL) not yet reported. We constructed a phage display antibody library from patient high anti-MDA-LDL isolated 3 IgG Fab antibodies, which specifically bound MDA-LDL. One these, IK17, also intact OxLDL well its lipid protein moieties but those native LDL. IK17 inhibited the uptake by macrophages apoptotic cells their phagocytosis macrophages. strongly immunostained necrotic cores human rabbit lesions. When 125 I-IK17 was injected intravenously into receptor-deficient mice, specific greatly enriched plaques versus normal aortic tissue. Human important biological properties that could influence natural course atherogenesis.