The online version of this article (doi:10.1186/1476-9255-9-42) contains supplementary material, which is available to authorized users.
Mi-Kyung Chang, Karsten Hartvigsen, Jewon Ryu contributed equally to this work.
The authors declare that they have no competing interests.
M-KC, Contributed to the conception and design of the study and to the acquisition, analysis and interpretation of data.KH, Contributed to preparation of the manuscript. JR, Contributed to the conception and design of the study and to the acquisition, analysis and interpretation of data. YK, Contributed to the conception and design of the study and to the acquisition, analysis and interpretation of data. KHH. Contributed to the conception and design of the study, to the acquisition, analysis and interpretation of data and to preparation of the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
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- The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine
Ki Hoon Han
- BioMed Central
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