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Peptidoglycan from Staphylococcus aureus induces tissue factor expression and procoagulant activity in human monocytes.

Mattsson, Eva LU ; Herwald, Heiko LU ; Björck, Lars LU and Egesten, Arne LU (2002) In Infection and Immunity 70(6). p.3033-3039
Abstract
Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. S. aureus can initiate blood coagulation, leading to the formation of microthrombi and multiorgan dysfunction in sepsis, whereas in endocarditis the bacterium induces fibrin clots on the inner surface of the heart, so-called endocardial vegetations. In the present study, we show that live and heat-killed S. aureus bacteria are potent inducers of procoagulant activity in human peripheral blood mononuclear cells. Furthermore, purified peptidoglycan, the main cell wall component of S. aureus, induced procoagulant activity in mononuclear cells in a concentration-dependent fashion. The procoagulant activity in these cells was dependent on expression... (More)
Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. S. aureus can initiate blood coagulation, leading to the formation of microthrombi and multiorgan dysfunction in sepsis, whereas in endocarditis the bacterium induces fibrin clots on the inner surface of the heart, so-called endocardial vegetations. In the present study, we show that live and heat-killed S. aureus bacteria are potent inducers of procoagulant activity in human peripheral blood mononuclear cells. Furthermore, purified peptidoglycan, the main cell wall component of S. aureus, induced procoagulant activity in mononuclear cells in a concentration-dependent fashion. The procoagulant activity in these cells was dependent on expression of tissue factor, since antibodies to tissue factor inhibited the effect of peptidoglycan. In mononuclear cells stimulated with peptidoglycan, reverse transcription-PCR showed tissue factor gene expression, and the gene product was detected by enzyme-linked immunosorbent assay. Finally, flow cytometry identified tissue factor at the surface of CD14-positive monocytes. Peptidoglycan is known to induce proinflammatory cytokine production in monocytes. The present investigation shows that peptidoglycan also activates the extrinsic pathway of coagulation by inducing the expression of tissue factor in these cells. This mechanism helps to explain the procoagulant activity, which plays such an important role in the pathogenicity of severe S. aureus infections. (Less)
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keywords
Mononuclear : cytology, Leukocytes, Mononuclear : drug effects, Mononuclear : microbiology, Thromboplastin : biosynthesis, Non-U.S. Gov't, Support, Staphylococcus aureus : metabolism, Peptidoglycan : pharmacology, Peptidoglycan : metabolism, Monocytes : physiology, Monocytes : microbiology, Monocytes : drug effects, Mononuclear : physiology, Lymphocytes : metabolism, Human, Coagulants : pharmacology, Coagulants : metabolism, Cell Adhesion, Blood Coagulation Factors
in
Infection and Immunity
volume
70
issue
6
pages
3033 - 3039
publisher
American Society for Microbiology
external identifiers
  • pmid:12010995
  • wos:000175761400038
  • scopus:0036259738
ISSN
1098-5522
DOI
10.1128/IAI.70.6.3033-3039.2002
language
English
LU publication?
yes
id
ed4b9ce4-30a8-4a29-8815-18e39aa13862 (old id 108274)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12010995&dopt=Abstract
date added to LUP
2007-07-10 08:25:41
date last changed
2017-06-18 03:31:26
@article{ed4b9ce4-30a8-4a29-8815-18e39aa13862,
  abstract     = {Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. S. aureus can initiate blood coagulation, leading to the formation of microthrombi and multiorgan dysfunction in sepsis, whereas in endocarditis the bacterium induces fibrin clots on the inner surface of the heart, so-called endocardial vegetations. In the present study, we show that live and heat-killed S. aureus bacteria are potent inducers of procoagulant activity in human peripheral blood mononuclear cells. Furthermore, purified peptidoglycan, the main cell wall component of S. aureus, induced procoagulant activity in mononuclear cells in a concentration-dependent fashion. The procoagulant activity in these cells was dependent on expression of tissue factor, since antibodies to tissue factor inhibited the effect of peptidoglycan. In mononuclear cells stimulated with peptidoglycan, reverse transcription-PCR showed tissue factor gene expression, and the gene product was detected by enzyme-linked immunosorbent assay. Finally, flow cytometry identified tissue factor at the surface of CD14-positive monocytes. Peptidoglycan is known to induce proinflammatory cytokine production in monocytes. The present investigation shows that peptidoglycan also activates the extrinsic pathway of coagulation by inducing the expression of tissue factor in these cells. This mechanism helps to explain the procoagulant activity, which plays such an important role in the pathogenicity of severe S. aureus infections.},
  author       = {Mattsson, Eva and Herwald, Heiko and Björck, Lars and Egesten, Arne},
  issn         = {1098-5522},
  keyword      = {Mononuclear : cytology,Leukocytes,Mononuclear : drug effects,Mononuclear : microbiology,Thromboplastin : biosynthesis,Non-U.S. Gov't,Support,Staphylococcus aureus : metabolism,Peptidoglycan : pharmacology,Peptidoglycan : metabolism,Monocytes : physiology,Monocytes : microbiology,Monocytes : drug effects,Mononuclear : physiology,Lymphocytes : metabolism,Human,Coagulants : pharmacology,Coagulants : metabolism,Cell Adhesion,Blood Coagulation Factors},
  language     = {eng},
  number       = {6},
  pages        = {3033--3039},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Peptidoglycan from Staphylococcus aureus induces tissue factor expression and procoagulant activity in human monocytes.},
  url          = {http://dx.doi.org/10.1128/IAI.70.6.3033-3039.2002},
  volume       = {70},
  year         = {2002},
}