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Related Experiment Videos

C-reactive protein does not directly induce tissue factor in human monocytes.

Elaine Paffen1, Hans L Vos, Rogier M Bertina

  • 1Hemostasis and Thrombosis Research Centre, Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands. epaffen@lumc.nl

Arteriosclerosis, Thrombosis, and Vascular Biology
|March 27, 2004
PubMed
Summary

C-reactive protein (CRP) does not directly induce tissue factor (TF) in monocytes or macrophages. However, CRP can indirectly induce TF expression in peripheral blood mononuclear cells (PBMCs), likely via cell-to-cell interactions.

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Area of Science:

  • Immunology
  • Hematology
  • Molecular Biology

Background:

  • C-reactive protein (CRP) is widely believed to initiate blood coagulation by inducing tissue factor (TF) synthesis in monocytes.
  • Understanding the precise mechanism of CRP-mediated TF expression is crucial for clarifying its role in thrombosis and inflammation.

Purpose of the Study:

  • To investigate the direct and indirect mechanisms of CRP-induced TF expression in monocytes and monocyte-derived macrophages (MDMs).
  • To determine if CRP directly stimulates TF synthesis in isolated monocytic cells.

Main Methods:

  • Isolated human monocytes and MDMs were cultured with varying concentrations and durations of CRP or lipopolysaccharide (LPS).
  • TF antigen and TF mRNA levels were quantified using established assays.

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  • Monocyte chemoattractant protein-1 (MCP-1) production and Fc receptor expression (FcRgammaII) were also assessed.
  • Experiments were extended to peripheral blood mononuclear cells (PBMCs) to evaluate indirect effects.

    • Main Results:

    • CRP (up to 100 microg/mL) did not significantly increase TF antigen or mRNA levels in purified monocytes or MDMs.
    • Lipopolysaccharide (LPS) strongly induced TF expression, serving as a positive control.
    • CRP did induce a 7-fold increase in MCP-1 production and monocytes expressed FcRgammaII.
    • CRP addition to PBMCs resulted in TF expression on monocytic cells, indicating an indirect effect.

    Conclusions:

    • CRP alone does not directly induce TF expression in purified monocytes and MDMs.
    • CRP's ability to induce TF expression in PBMCs suggests an indirect mechanism involving interactions with other blood cells.
    • These findings challenge the direct role of CRP in initiating TF-mediated coagulation in monocytes and highlight the importance of cellular crosstalk.