Objective-It is generally assumed that C-reactive protein (CRP) induces synthesis of tissue factor (TF) in monocytic cells, thereby potentially initiating intravascular blood coagulation. We aimed to elucidate the mechanism of CRP-induced TF expression in monocytes and monocyte-derived macrophages (MDMs) in vitro. Methods and Results-Monocytes were isolated from the blood of healthy donors and cultured with or without CRP or lipopolysaccharide (LPS) to study the time course of TF antigen and TF mRNA expression. Addition of 100 g/mL CRP did not result in a significant increase in TF antigen (range: 9 to 163 pg/10 6 cells, nϭ11) and TF mRNA (relative number of TF transcripts; N TF ϭ0.01 to 0.33), when compared with nonstimulated cells (TF antigen 7 to 46 pg/10 6 cells, N TF ϭ0.01 to 0.13). Variation of CRP concentration and exposure time did not affect the TF response. Similar results were obtained in monocytes cultured in suspension and in MDMs. In contrast, TF was strongly induced by 10 g/mL LPS (TF antigen 1125 to 6120 pg/10 6 cells, N TF ϭ5.94 to 23.43). Cultured monocytes did express FcR␥II, a putative CRP receptor, and addition of CRP induced a 7-fold increase in the production of monocyte chemoattractant protein-1 (MCP-1). Interestingly, CRP addition to peripheral blood mononuclear cells (PBMCs) did result in TF expression on monocytic cells.
Conclusions-The