OxLDL-IgG immune complexes induce survival of human monocytes.
OBJECTIVE
Immune complexes containing oxidatively modified low-density lipoprotein (oxLDL) particles are deposited in human atherosclerotic lesions during atherogenesis. Here we studied whether OxLDL-IgG immune complexes (OxLDL-IgG ICs) affect survival of human monocytes.


RESULTS
As demonstrated by light microscopy, and analysis of cell proliferation, caspase-3 activity, and DNA fragmentation, OxLDL-IgG ICs promoted survival of cultured human monocytes by decreasing their spontaneous apoptosis. OxLDL-IgG ICs induced a concentration-dependent production of the major monocyte growth factor, monocyte colony-stimulating factor (M-CSF), by the monocytes, but its inhibition was without effect on OxLDL-IgG IC-induced monocyte survival. Rather, OxLDL-IgG ICs induced rapid phosphorylation of Akt, suggesting a direct anti-apoptotic effect mediated by cross-linking of Fcgamma receptors. Experiments with receptor blocking antibodies revealed that the OxLDL-IgG IC-induced monocyte survival was mediated by Fcgamma receptor I.


CONCLUSIONS
The results show that OxLDL-IgG ICs promote survival of monocytes by cross-linking Fcgamma receptor I and activating Akt-dependent survival signaling. The results reveal a novel mechanism by which an immune reaction toward oxLDL can play a role in the accumulation of macrophages in human atherosclerotic lesions.
Oksjoki
Riina
R
Wihuri Research Institute, Helsinki, Finland.
Kovanen
Petri T
PT
Lindstedt
Ken A
KA
Jansson
Bo
B
Pentikäinen
Markku O
MO
D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
D000936:Antigen-Antibody Complex; D003432:Cross-Linking Reagents; C489017:FCGR1A protein, human; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; C099252:oxidized low density lipoprotein; D016173:Macrophage Colony-Stimulating Factor; D051057:Proto-Oncogene Proteins c-akt