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on December 22, 2005

Arteriosclerosis, Thrombosis, and Vascular Biology. 2005
Published online before print December 22, 2005, doi: 10.1161/01.ATV.0000201041.14438.8d
A more recent version of this article appeared on March 1, 2006
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Submitted on July 13, 2005
Accepted on December 3, 2005

OxLDL-IgG Immune Complexes Induce Survival of Human Monocytes

Riina Oksjoki ; Petri T. Kovanen *; Ken A. Lindstedt ; Bo Jansson ; and 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.

* To whom correspondence should be addressed. 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 (CSF) (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{gamma} receptors. Experiments with receptor blocking antibodies revealed that the OxLDL-IgG IC-induced monocyte survival was mediated by Fc{gamma} receptor I.

Conclusions--The results show that OxLDL-IgG ICs promote survival of monocytes by cross-linking Fc{gamma} 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.
Key words: atherosclerosis • monocytes • oxLDL




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