Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL

Immune complexes (IC) prepared with human low density lipoprotein (LDL) and rabbit LDL antibodies induce foam cell transformation of human macrophages and activate the release of proinflammatory mediators by human macrophages and THP-1 cells. Because the affinity of human oxidized LDL (oxLDL) antibo...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 105(2002), 1 vom: 30. Okt., Seite 81-92
1. Verfasser: Virella, G (VerfasserIn)
Weitere Verfasser: Atchley, D, Koskinen, Sinikka, Zheng, D, Lopes-Virella, Maria F, DCCT/EDIC Research Group
Format: Aufsatz
Sprache:English
Veröffentlicht: 2002
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Antigen-Antibody Complex Immunoglobulin Isotypes Lipoproteins, LDL Tumor Necrosis Factor-alpha oxidized low density lipoprotein Cholesterol 97C5T2UQ7J
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100 1 |a Virella, G  |e verfasserin  |4 aut 
245 1 0 |a Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL 
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520 |a Immune complexes (IC) prepared with human low density lipoprotein (LDL) and rabbit LDL antibodies induce foam cell transformation of human macrophages and activate the release of proinflammatory mediators by human macrophages and THP-1 cells. Because the affinity of human oxidized LDL (oxLDL) antibodies is lower than that of rabbit antibodies, IC formed with human antibodies could have limited pathogenic potential. Immune complexes prepared with human oxidized LDL (oxLDL) and purified human oxLDL antibodies (predominantly of the IgG1 and IgG3 isotypes) were presented to THP-1 cells using two protocols previously described in studies of the properties of LDL-IC prepared with rabbit antibodies. OxLDL/human oxLDL antibody IC immobilized by adsorption to red blood cells (RBC) induced the release of significantly higher levels of TNF from THP-1 cells (872-313 pg/ml) than oxLDL adsorbed to RBC (461-75.6 pg/ml) and caused a higher degree of cholesterol ester accumulation in the same cells (5.4-0.77 in cells incubated with IC-coated RBC vs 1.99-1.16 in oxLDL-coated RBC). Insoluble IC prepared with oxLDL/human oxLDL antibody were even more effective in promoting intracellular accumulation of cholesterol in THP-1 cells (total cholesterol = 53.8-13.5 and cholesterol esters = 24.0-7.2 mg/l in THP-1 cells incubated with insoluble IC (200 micrograms) vs total cholesterol = 32.4-8.2 and cholesterol esters = 7.7 +/- 2.8 micrograms/l in THP-1 cells incubated with an identical concentration of oxLDL) and also induced the release of TNF. Thus we have demonstrated that IC prepared with human oxLDL and human oxLDL antibodies have the same atherogenic and proinflammatory properties as IC prepared with human LDL and rabbit LDL antibodies. This strongly supports the concept that modified LDL-IC present in circulation and/or tissues play an important pathogenic role in arteriosclerosis 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, Non-P.H.S. 
650 4 |a Research Support, U.S. Gov't, P.H.S. 
650 7 |a Antigen-Antibody Complex  |2 NLM 
650 7 |a Immunoglobulin Isotypes  |2 NLM 
650 7 |a Lipoproteins, LDL  |2 NLM 
650 7 |a Tumor Necrosis Factor-alpha  |2 NLM 
650 7 |a oxidized low density lipoprotein  |2 NLM 
650 7 |a Cholesterol  |2 NLM 
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700 1 |a Atchley, D  |e verfasserin  |4 aut 
700 1 |a Koskinen, Sinikka  |e verfasserin  |4 aut 
700 1 |a Zheng, D  |e verfasserin  |4 aut 
700 1 |a Lopes-Virella, Maria F  |e verfasserin  |4 aut 
700 0 |a DCCT/EDIC Research Group  |e verfasserin  |4 aut 
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