J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M600064-JLR200 on June 27, 2006

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Journal of Lipid Research, Vol. 47, 1975-1983, September 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages

Antonio F. Saad*,{dagger}, Gabriel Virella§, Charlyne Chassereau*,{dagger}, Robert J. Boackle** and Maria F. Lopes-Virella1,*,{dagger}

* Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC
{dagger} Department of Medicine, Division of Endocrinology-Metabolism-Nutrition, Medical University of South Carolina, Charleston, SC
§ Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC
** College of Dental Medicine, Department of Stomatology, Medical University of South Carolina, Charleston, SC

Published, JLR Papers in Press, June 27, 2006.

1 To whom correspondence should be addressed. e-mail: virellam{at}musc.edu

Oxidized low density lipoprotein (OxLDL) is immunogenic and induces autoimmune responses in humans. OxLDL antibodies are predominantly of the proinflammatory IgG1 and IgG3 isotypes. We tested the capacity of immune complexes prepared with copper-oxidized human LDL and affinity chromatography-purified human OxLDL antibodies [OxLDL-immune complexes (ICs)] to activate complement and to induce cytokine release by MonoMac 6 (MM6) cells and by primary human macrophages. The levels of C4d and C3a were significantly higher in human serum incubated with OxLDL-ICs than after incubation with OxLDL or OxLDL antibody, indicating complement activation by the classical pathway. MM6 cells and primary human macrophages were incubated with OxLDL-ICs, with or without prior conditioning with interferon-{gamma}. After 18 h of incubation, both MM6 cells and primary human macrophages released significantly higher levels of proinflammatory cytokines after incubation with OxLDL-ICs than after incubation with OxLDL or with OxLDL antibody, both in primed and unprimed cells. OxLDL-ICs were more potent activators of MM6 cells than keyhole limpet hemocyanin-ICs. Blocking Fc gamma receptor I (Fc{gamma}RI) with monomeric IgG1 significantly depressed the response of MM6 cells to OxLDL-ICs. In conclusion, human OxLDL-ICs have proinflammatory properties, as reflected by their capacity to activate the classical pathway of complement and to induce proinflammatory cytokine release from MM6 cells and primary human macrophages.

Supplementary key words oxidized low density lipoprotein • autoimmunity • atherosclerosis • activated macrophages • inflammation • oxidized low density lipoprotein immune complexes • oxidized low density lipoprotein antibodies


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