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Infection and Immunity, June 2002, p. 3033-3039, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.3033-3039.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Peptidoglycan from Staphylococcus aureus Induces Tissue Factor Expression and Procoagulant Activity in Human Monocytes

Department of Medical Microbiology, Dermatology, and Infection,¹ Department of Cell and Molecular Biology, Lund University, Lund,² Department of Medical Microbiology, Lund University, Malmö University Hospital, Malmö, Sweden³

Received 13 December 2001/ Returned for modification 15 January 2002/ Accepted 14 March 2002

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.

Editor: D. L. Burns

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