C-Reactive Protein Does Not Directly Induce Tissue Factor in Human Monocytes

Abstract

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 μg/mL CRP did not result in a significant increase in TF antigen (range: 9 to 163 pg/106 cells, n=11) and TF mRNA (relative number of TF transcripts; NTF=0.01 to 0.33), when compared with nonstimulated cells (TF antigen 7 to 46 pg/106 cells, NTF=0.01 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 μg/mL LPS (TF antigen 1125 to 6120 pg/106 cells, NTF=5.94 to 23.43). Cultured monocytes did express FcRγII, 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 absence of TF induction after incubation of purified monocytes with CRP indicates that CRP is unable to induce TF expression in monocytes and MDMs directly. The presence of CRP-induced TF expression in PBMCs suggests that CRP can induce TF indirectly, probably through cross-talk between cells.