Background; Both C-reactive protein (CRP) and oxidized LDL (oxLDL) trigger pro-inflammatory activities by macrophages during the process of atherosclerosis. We previously reported that CRP calcium-dependently binds oxLDL in vitro. However, the functional relevance of the complex formation is not clear. Results; 1. Chemiluminescent immunoassay and HPLC confirmed that lysophosphatidylcholine (LPC), a main phosphorylcholine (PC)-bearing component of oxLDL, formed calcium-dependent stable complexes with CRP. 2. CRP binding assay using Fc款RIa- or Fc款RIIa-transfected 293FTcells showed that Kd values of CRP-LPC complexes (CRP/LPC) binding to Fc款RIa and Fc款RIIa were 5-20 fold higher than that of CRP binding. Moreover, confocal microscopic image analysis showed that CRP and LPC maintain their complex forms in the cytosol of THP-1 monocyte-derived macrophages. 4. Promoter assay showed that the magnitude of NF觀B activation elicited by CRP/LPC was significantly lower than those by CRP or LPC alone. On the other hand, same analysis showed that the degree of PPAR款 activation induced by oxidized linoleic acid, which does not bind CRP, was not affected by the addition of CRP. 5. EMSA and confocal microscopic image analysis of H2DCFDA-labeled human macrophages further showed that the magnitude of AP-1 activation and ROS production elicited by CRP/LPC complexes were significantly lower than those by CRP or LPC alone, too. Moreover, the mRNA expression levels of MCP-1, MMPs, interleukin-1棺 and interleukin-6, as determined by real-time PCR, by CRP/LPC-treated human macrophages were less prominent when compared with those elicited by CRP or LPC alone. Conclusions; We conclude that the complex formation between CRP and oxLDL, most notably PC (+) LPC, selectively suppresses pro-inflammatory properties of either CRP or LPC, which may protect macrophages in the atherosclerotic wall from full-blown inflammatory and oxidative insults.