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Titolo:
Human-derived anti-oxidized LDL autoantibody blocks uptake of oxidized LDLby macrophages and localizes to atherosclerotic lesions in vivo
Autore:
Shaw, PX; Horkko, S; Tsimikas, S; Chang, MK; Palinski, W; Silverman, GJ; Chen, PP; Witztum, JL;
Indirizzi:
Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 pt Med, La Jolla, CA 92093 USA Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA Univ Calif Los Angeles Los Angeles CA USA Dept Med, Los Angeles, CA USA
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 8, volume: 21, anno: 2001,
pagine: 1333 - 1339
SICI:
1079-5642(200108)21:8<1333:HALABU>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; MOUSE PERITONEAL-MACROPHAGES; OXIDATION-SPECIFIC EPITOPES; MONOCLONAL-ANTIBODIES; DEFICIENT MICE; APOPTOTIC CELLS; COMBINATORIAL LIBRARY; DNA AUTOANTIBODIES; PROTEIN ADDUCTS; HIGH TITERS;
Keywords:
atherosclerosis; imaging; antibodies; lipoproteins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Witztum, JL Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA Univ Calif San Diego 9500 Gilman Dr La Jolla CA USA 92093 USA
Citazione:
P.X. Shaw et al., "Human-derived anti-oxidized LDL autoantibody blocks uptake of oxidized LDLby macrophages and localizes to atherosclerotic lesions in vivo", ART THROM V, 21(8), 2001, pp. 1333-1339

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 autoandbodies 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 apoptoticcells and inhibited their phagocytosis by macrophages. IK17 strongly immunostained necrotic cores of human and rabbit atherosclerotic lesions. When I-125-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.

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Documento generato il 02/04/20 alle ore 08:20:02