Interferon-gamma and lipopolysaccharide potentiate monocyte tissue factor induction by C-reactive protein: relationship with age, sex, and hormone replacement treatment.
BACKGROUND
Elevated plasma levels of C-reactive protein (CRP) in population studies and in patients with unstable coronary syndromes are predictive of future adverse events, including cardiac death and myocardial infarction, implicating inflammation in pathogenesis. Although CRP is considered a marker of inflammation, it induces monocyte tissue factor (TF) and may play a prothrombotic role in atherosclerosis and its complications.


RESULTS
Peripheral blood mononuclear cells (PBMCs) from 79 healthy men and women aged 26 to 83 years and 21 healthy postmenopausal women taking hormone replacement therapy (HRT) were stimulated with CRP, lipopolysaccharide (LPS), interferon-gamma (IFN), or their combination. Levels of CRP in the normal range (1 to 5 microg/mL) increased basal monocyte TF 4- to 6-fold and 40-fold at higher concentrations (25 microg/mL). Coincubation of LPS with CRP produced a greater-than-additive response. IFN did not induce TF but synergized with CRP to approximately double activity. There was a striking positive correlation between age and monocyte TF induction, with a dramatic rise on monocytes from postmenopausal women that was not apparent on cells from women taking HRT.


CONCLUSIONS
Synergy between CRP and inflammatory mediators may play a direct prothrombotic role in the pathogenesis of coronary atherosclerosis and its acute complications by increasing monocyte/macrophage TF. This may contribute to age and sex differences in coronary events and to the protective effects of HRT.
Nakagomi
A
A
School of Pathology, University of New South Wales, Concord Hospital, Australia.
Freedman
S B
SB
Geczy
C L
CL
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000378:metabolism* / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D017698:Postmenopause; D012737:Sex Factors; D013925:Thromboplastin / Q000187:drug effects* / Q000378:metabolism
D008070:Lipopolysaccharides; D007371:Interferon-gamma; D002097:C-Reactive Protein; D013925:Thromboplastin