C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor

Jaroslav Cermak, Nigel S. Key, Ronald R. Bach, J. Balla, Harry S. Jacob, Gregory M. Vercellotti

Research output: Contribution to journalArticle

708 Citations (Scopus)

Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)513-520
Number of pages8
JournalBlood
Volume82
Issue number2
Publication statusPublished - Jul 15 1993

Fingerprint

Thromboplastin
C-Reactive Protein
Monocytes
Blood
Blood Cells
Immunoglobulin G
Horseshoe Crabs
Polymyxin B
Acute-Phase Proteins
Disseminated Intravascular Coagulation
Endothelial cells
Human Umbilical Vein Endothelial Cells
Dactinomycin
Cycloheximide
Coagulation
Human Activities
Endotoxins
Refractory materials
Assays
Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Cermak, J., Key, N. S., Bach, R. R., Balla, J., Jacob, H. S., & Vercellotti, G. M. (1993). C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood, 82(2), 513-520.

C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. / Cermak, Jaroslav; Key, Nigel S.; Bach, Ronald R.; Balla, J.; Jacob, Harry S.; Vercellotti, Gregory M.

In: Blood, Vol. 82, No. 2, 15.07.1993, p. 513-520.

Research output: Contribution to journalArticle

Cermak, J, Key, NS, Bach, RR, Balla, J, Jacob, HS & Vercellotti, GM 1993, 'C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor', Blood, vol. 82, no. 2, pp. 513-520.
Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood. 1993 Jul 15;82(2):513-520.
Cermak, Jaroslav ; Key, Nigel S. ; Bach, Ronald R. ; Balla, J. ; Jacob, Harry S. ; Vercellotti, Gregory M. / C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. In: Blood. 1993 ; Vol. 82, No. 2. pp. 513-520.
@article{3a512aa2fdbc470aa6bd0c18ef10d1a6,
title = "C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor",
abstract = "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 μg/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.",
author = "Jaroslav Cermak and Key, {Nigel S.} and Bach, {Ronald R.} and J. Balla and Jacob, {Harry S.} and Vercellotti, {Gregory M.}",
year = "1993",
month = "7",
day = "15",
language = "English",
volume = "82",
pages = "513--520",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor

AU - Cermak, Jaroslav

AU - Key, Nigel S.

AU - Bach, Ronald R.

AU - Balla, J.

AU - Jacob, Harry S.

AU - Vercellotti, Gregory M.

PY - 1993/7/15

Y1 - 1993/7/15

N2 - 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 μg/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.

AB - 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 μg/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.

UR - http://www.scopus.com/inward/record.url?scp=0027162435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027162435&partnerID=8YFLogxK

M3 - Article

VL - 82

SP - 513

EP - 520

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -