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

Antonio Saad, Gabriel Virella, Charlyne Chassereau, Robert J. Boackle, Maria F. Lopes-Virella

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1975-1983
Number of pages9
JournalJournal of Lipid Research
Volume47
Issue number9
DOIs
StatePublished - Sep 22 2006
Externally publishedYes

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Macrophages
Antigen-Antibody Complex
Cytokines
Classical Complement Pathway
Antibodies
Immunoglobulin G
oxidized low density lipoprotein
Affinity chromatography
IgG Receptors
Autoimmunity
Affinity Chromatography
Interferons
Copper

Keywords

  • Activated macrophages
  • Atherosclerosis
  • Autoimmunity
  • Inflammation
  • Oxidized low density lipoprotein
  • Oxidized low density lipoprotein antibodies
  • Oxidized low density lipoprotein immune complexes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. / Saad, Antonio; Virella, Gabriel; Chassereau, Charlyne; Boackle, Robert J.; Lopes-Virella, Maria F.

In: Journal of Lipid Research, Vol. 47, No. 9, 22.09.2006, p. 1975-1983.

Research output: Contribution to journalArticle

Saad, Antonio ; Virella, Gabriel ; Chassereau, Charlyne ; Boackle, Robert J. ; Lopes-Virella, Maria F. / OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. In: Journal of Lipid Research. 2006 ; Vol. 47, No. 9. pp. 1975-1983.
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AB - 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.

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