(Circulation. 2000;101:1785.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Interferon-
and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by C-Reactive Protein
Relationship With Age, Sex, and Hormone Replacement Treatment
From the School of Pathology, University of New South Wales (A.N., C.L.G.), and the Department of Cardiology, Concord Hospital, University of Sydney, Australia (S.B.F).
Correspondence to Carolyn Geczy, School of Pathology, University New South Wales, NSW 2052, Australia. E-mail c.geczy{at}unsw.edu.au
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.
Methods and 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-
(IFN), or their combination. Levels of CRP in the normal
range (1 to 5 µg/mL) increased basal monocyte TF 4- to 6-fold and
40-fold at higher concentrations (25 µg/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.
Key Words: inflammation • coagulation • immune system • atherosclerosis • coronary disease
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