Importance of C-reactive protein in regulating monocyte tissue factor expression in patients with inflammatory rheumatic diseases.
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, ss2-glycoprotein I (ss2-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 ss2-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 ss2-GPI. Significantly more TF was induced with CRP combined with ss2-GPI, compared to ss2-GPI alone, either with costimulation or CRP priming. Conversely, when combined with LPS, ss2-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.


CONCLUSIONS
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 ss2-GPI) was apparent, and ss2-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 vascular disease seen in patients with IRD.
Cai
Hong
H
Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales (UNSW), Australia.
Song
Changjie
C
Lim
Irwin Geok San
IG
Krilis
Steven A
SA
Geczy
Carolyn L
CL
McNeil
H Patrick
HP
D000328:Adult; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology; D053482:beta 2-Glycoprotein I
D006023:Glycoproteins; D008070:Lipopolysaccharides; D053482:beta 2-Glycoprotein I; D002097:C-Reactive Protein; D013925:Thromboplastin