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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:576.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

OxLDL–IgG Immune Complexes Induce Survival of Human Monocytes

Riina Oksjoki; Petri T. Kovanen; Ken A. Lindstedt; Bo Jansson; Markku O. Pentikäinen

From Wihuri Research Institute (R.O., P.T.K., K.A.L., M.O.P.), Helsinki, Finland, and BioInvent International AB (B.J.), Lund, Sweden.

Correspondence to Petri T. Kovanen, Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland. E-mail petri.kovanen{at}wri.fi

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 Fc receptors. Experiments with receptor blocking antibodies revealed that the OxLDL–IgG IC–induced monocyte survival was mediated by Fc receptor I.

Conclusions— The results show that OxLDL–IgG ICs promote survival of monocytes by cross-linking Fc 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.

Immune complexes containing oxidatively modified low-density lipoprotein (oxLDL) particles are deposited in human atherosclerotic lesions during atherogenesis. Here we show that OxLDL–IgG immune complexes (OxLDL–IgG ICs) promote the survival of monocytes, independently of produced M-CSF, by cross-linking Fc receptor I and activating Akt-dependent survival signaling.

Key Words: atherosclerosis • monocytes • oxLDL

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