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Previous Article | Table of Contents | Next Article 
C-reactive protein induces human peripheral blood monocytes to synthesize
tissue factor
J Cermak, NS Key, RR Bach, J Balla, HS Jacob and GM Vercellotti
Department of Medicine, University of Minnesota, Minneapolis 55455.
The acute inflammatory response is frequently accompanied by serious
thrombotic events. We show that C-reactive protein (CRP), an acute- phase
reactant that markedly increases its serum concentration in response to
inflammatory stimuli, induced monocytes to express tissue factor (TF), a
potent procoagulant. Purified human CRP in concentrations commonly achieved
in vivo during inflammation (10 to 100 micrograms/mL) induced a 75-fold
increase in TF procoagulant activity (PCA) of human peripheral blood
mononuclear cells (PBM), with a parallel increase in TF antigen levels.
CRP-induced PCA was completely blocked by a monoclonal antibody against
human TF but not by irrelevant murine IgG. Dot blot analysis showed a
significant increase of TF mRNA after 4 hours of incubation with CRP,
followed by a peak of PCA within 6 and 8 hours. Actinomycin D and
cycloheximide blocked CRP-stimulated PCA, suggesting that de novo TF
protein synthesis was required. Endotoxin (LPS) contamination of CRP was
excluded as the mediator of TF synthesis because: (1) CRP was Limulus assay
negative; (2) induction of TF PCA by CRP was not blocked by Polymyxin B, in
contrast to LPS- induced PCA; (3) antihuman CRP IgG inhibited CRP-induced
PCA, but not LPS-induced PCA; (4) CRP was able to stimulate TF production
in LPS- pretreated PBM refractory to additional LPS stimulation; and, (5)
unlike LPS, CRP was incapable of inducing TF in human umbilical vein
endothelial cells. We suggest that CRP-mediated TF production in monocytes
may contribute to the development of disseminated intravascular coagulation
and thrombosis in inflammatory states.
Volume 82,
Issue 2,
pp. 513-520,
07/15/1993
Copyright © 1993 by The American Society of Hematology

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