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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:975.)
© 2004 American Heart Association, Inc.

Thrombosis

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

Elaine Paffen; Hans L. Vos; Rogier M. Bertina

From the Hemostasis and Thrombosis Research Centre, Department of Hematology, Leiden University Medical Centre, Leiden, the Netherlands.

Correspondence to Elaine Paffen, Hemostasis and Thrombosis Research Centre, Department of Hematology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. E-mail epaffen{at}lumc.nl

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; N_TF=0.01 to 0.33), when compared with nonstimulated cells (TF antigen 7 to 46 pg/10⁶ cells, N_TF=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, N_TF=5.94 to 23.43). Cultured monocytes did express FcRII, 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.

Key Words: C-reactive protein • tissue factor • monocytes • MCP-1 • atherosclerosis

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