Human-Derived Anti-Oxidized LDL Autoantibody Blocks Uptake of Oxidized LDL by Macrophages and Localizes to Atherosclerotic Lesions In Vivo
Aging
Arteriosclerosis
Lipoproteins
Clinical Sciences
610
Clinical sciences
Cardiorespiratory Medicine and Haematology
Cardiovascular
Cardiovascular medicine and haematology
Antibodies
LDL
Epitopes
Immunoglobulin Fab Fragments
03 medical and health sciences
0302 clinical medicine
Cardiovascular Medicine and Haematology
Malondialdehyde
Monoclonal
2.1 Biological and endogenous factors
antibodies
Animals
Humans
Autoantibodies
Biomedical and Clinical Sciences
Macrophages
imaging
Antibodies, Monoclonal
Atherosclerosis
3. Good health
lipoproteins
Lipoproteins, LDL
Cardiovascular System & Hematology
atherosclerosis
Biotechnology
DOI:
10.1161/hq0801.093587
Publication Date:
2007-09-28T18:27:24Z
AUTHORS (8)
ABSTRACT
Autoantibodies to oxidation-specific epitopes of low density lipoprotein (LDL), such as malondialdehyde-modified LDL (MDA-LDL), occur in plasma and atherosclerotic lesions of humans and animals. Plasma titers of such antibodies are correlated with atherosclerosis in murine models, and several such autoantibodies have been cloned. However, human-derived monoclonal antibodies to epitopes of oxidized LDL (OxLDL) have not yet been reported. We constructed a phage display antibody library from a patient with high plasma anti-MDA-LDL titers and isolated 3 monoclonal IgG Fab antibodies, which specifically bound to MDA-LDL. One of these, IK17, also bound to intact OxLDL as well as to its lipid and protein moieties but not to those of native LDL. IK17 inhibited the uptake of OxLDL by macrophages and also bound to apoptotic cells and inhibited their phagocytosis by macrophages. IK17 strongly immunostained necrotic cores of human and rabbit atherosclerotic lesions. When
125
I-IK17 was injected intravenously into LDL receptor-deficient mice, its specific uptake was greatly enriched in atherosclerotic plaques versus normal aortic tissue. Human autoantibodies to OxLDL have important biological properties that could influence the natural course of atherogenesis.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (34)
CITATIONS (166)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....