Importance of C-reactive protein in regulating monocyte tissue factor expression in patients with inflammatory rheumatic diseases

Hong Cai, Changjie Song, Irwin Geok San Lim, Steven A. Krilis, Carolyn L. Geczy, H. Patrick McNeil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Objective. To determine the relationship between plasma C-reactive protein (CRP) concentrations and monocyte tissue factor (TF) expression induced in vitro by combinations of CRP, β2-glycoprotein I (β2- GPI), and lipopolysaccharide (LPS). Methods. Peripheral blood mononuclear cells (PBMC) from 26 healthy individuals and 31 patients with inflammatory rheumatic diseases (IRD) were cultured with combinations of CRP, purified or recombinant β2-GPI, and LPS and monocyte TF procoagulant activity, TF antigen, and TF mRNA were measured. Results were examined against plasma CRP levels. Results. Monocytes from patients with IRD expressed significantly more TF when stimulated with CRP compared to normal monocytes (p = 0.002). An incremental positive correlation was observed between plasma CRP levels and TF induced by CRP or β2-GPI. Significantly more TF was induced with CRP combined with β2-GPI, compared to β2-GPI alone, either with costimulation or CRP priming. Conversely, when combined with LPS, β2-GPI suppressed TF induction in a dose-dependent manner on normal PBMC but not on PBMC from patients with IRD. The loss of suppression correlated strongly with plasma CRP levels. Conclusion. This study shows a remarkably consistent effect of CRP on monocyte TF expression. Systemic inflammation associated with elevated plasma CRP conferred a phenotype on PBMC, whereby incremental priming with respect to TF expression (induced by CRP itself or β2-GPI) was apparent, and β2-GPI-mediated inhibition of TF expression induced by LPS was incrementally lost. CRP regulation of monocyte TF could contribute to the higher than expected atherosclerotic vascu-lar disease seen in patients with IRD.

Original languageEnglish
Pages (from-to)1224-1231
Number of pages8
JournalJournal of Rheumatology
Volume32
Issue number7
Publication statusPublished - Jul 2005
Externally publishedYes

Keywords

  • C-reactive protein
  • Rheumatoid arthritis
  • Thromboplastin

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