OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages
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-purifie...
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| Format: | Article |
| Language: | English |
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Elsevier
2006-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520434649 |
| _version_ | 1818384697578749952 |
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| author | Antonio F. Saad Gabriel Virella Charlyne Chassereau Robert J. Boackle Maria F. Lopes-Virella |
| author_facet | Antonio F. Saad Gabriel Virella Charlyne Chassereau Robert J. Boackle Maria F. Lopes-Virella |
| author_sort | Antonio F. Saad |
| collection | DOAJ |
| description | 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-γ. 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 (FcγRI) 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. |
| first_indexed | 2024-12-14T03:26:23Z |
| format | Article |
| id | doaj.art-c562a1d17997482aadb3da205c0a85ad |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:26:23Z |
| publishDate | 2006-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c562a1d17997482aadb3da205c0a85ad2022-12-21T23:18:53ZengElsevierJournal of Lipid Research0022-22752006-09-0147919751983OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophagesAntonio F. Saad0Gabriel Virella1Charlyne Chassereau2Robert J. Boackle3Maria F. Lopes-Virella4Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC; Department of Medicine, Division of Endocrinology-Metabolism-Nutrition, Medical University of South Carolina, Charleston, SCDepartment of Microbiology and Immunology, Medical University of South Carolina, Charleston, SCRalph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC; Department of Medicine, Division of Endocrinology-Metabolism-Nutrition, Medical University of South Carolina, Charleston, SCCollege of Dental Medicine, Department of Stomatology, Medical University of South Carolina, Charleston, SCRalph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC; Department of Medicine, Division of Endocrinology-Metabolism-Nutrition, Medical University of South Carolina, Charleston, SCOxidized 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-γ. 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 (FcγRI) 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.http://www.sciencedirect.com/science/article/pii/S0022227520434649oxidized low density lipoproteinautoimmunityatherosclerosisactivated macrophagesinflammationoxidized low density lipoprotein immune complexes |
| spellingShingle | Antonio F. Saad Gabriel Virella Charlyne Chassereau Robert J. Boackle Maria F. Lopes-Virella OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages Journal of Lipid Research oxidized low density lipoprotein autoimmunity atherosclerosis activated macrophages inflammation oxidized low density lipoprotein immune complexes |
| title | OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages |
| title_full | OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages |
| title_fullStr | OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages |
| title_full_unstemmed | OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages |
| title_short | OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages |
| title_sort | oxldl immune complexes activate complement and induce cytokine production by monomac 6 cells and human macrophages |
| topic | oxidized low density lipoprotein autoimmunity atherosclerosis activated macrophages inflammation oxidized low density lipoprotein immune complexes |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520434649 |
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