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Open Access Research

The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine

Mi-Kyung Chang13, Karsten Hartvigsen1, Jewon Ryu2, Yuna Kim2 and Ki Hoon Han2*

Author Affiliations

1 Department of Medicine, University of California San Diego, La Jolla, CA, USA

2 University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-2 dong Songpa-gu 138-736, Seoul, South Korea

3 Present address: Bayer Korea, 7th fl. Samsung-Boramae Omni Tower, 395-62, Sindaebang dong Dongzak-gu, Seoul, South Korea

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Journal of Inflammation 2012, 9:42  doi:10.1186/1476-9255-9-42

Published: 31 October 2012

Abstract

Rationale

C-reactive protein (CRP) and lysophosphatidylcholine (LPC) are phosphorylcholine-(PC)-containing oxidized phospholipids (oxPLs) found in oxidized LDL (oxLDL), which trigger pro-atherogenic activities of macrophages during the process of atherosclerosis. It has been previously reported that CRP binds to the PC head group of oxLDL in a calcium-dependent manner. The aim of this study was to investigate the importance of binding between CRP and LPC to the pro-atherogenic activities of macrophages.

Objectives and findings

A chemiluminescent immunoassay and HPLC showed that human recombinant CRP formed a stable complex with LPC in the presence of calcium. The Kd value of the binding of the CRP-LPC complex to the receptors FcγRIA or FcγRIIA was 3–5 fold lower than that of CRP alone. The CRP-LPC complex triggered less potent generation of reactive oxygen species and less activation of the transcription factors AP-1 and NF-kB by human monocyte-derived macrophages in comparison to CRP or LPC alone. However, CRP did not affect activities driven by components of oxLDL lacking PC, such as upregulation of PPRE, ABCA1, CD36 and PPARγ and the enhancement of cholesterol efflux by human macrophages. The presence of CRP inhibited the association of Dil-labelled oxLDL to human macrophages.

Conclusions

The formation of complexes between CRP and PC-containing oxPLs, such as LPC, suppresses the pro-atherogenic effects of CRP and LPC on macrophages. This effect may in part retard the progression of atherosclerosis.

Keywords:
C-reactive protein; Lysophosphatidylcholine; Macrophages; Foam cells