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. METHODS AND 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.