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Infection and Immunity, November 1999, p. 6130-6138, Vol. 67, No. 11
Department of Infectious Diseases, Leiden
University Medical Center, Leiden, The Netherlands
Received 28 May 1999/Returned for modification 22 July
1999/Accepted 31 August 1999
A cardinal process in bacterial endocarditis (BE) is the activation
of the clotting system and the formation of a fibrin clot on the inner
surface of the heart, the so-called endocardial vegetation. The
processes that lead to the activation of the clotting system on
endothelial surfaces upon exposure to bacteria are largely unknown. In
the present study, we investigated in an in vitro model whether
infection of human endothelial cells (EC) with bacteria that are
relevant to BE, such as Staphylococcus aureus,
Streptococcus sanguis, and Staphylococcus
epidermidis, leads to induction of tissue factor (TF)-dependent
procoagulant activity (TFA) and whether this process is influenced by
host factors, such as interleukin-1 (IL-1), that are produced in
response to the bacteremia in vivo. The results show that S. aureus binds to and is internalized by EC, resulting in
expression of TF mRNA and TF surface protein as well as generation of
TFA within 4 to 8 h after infection. No TFA was found when EC were
exposed to UV-irradiated S. aureus or bacterial cell wall
fragments. S. sanguis and S. epidermidis, although also binding to EC, did not induce endothelial TFA. This indicates a species and strain dependency. EC also expressed TFA after
exposure to IL-1. The enhanced TFA of EC after exposure to S. aureus was not prevented by IL-1 receptor antagonist, arguing against an auto- or paracrine contribution of endogenous IL-1. When
IL-1 was applied together with bacteria, this had a synergistic effect
on the induction of EC TFA. This was found in particular with S. aureus but also, although to a lesser degree, with S. sanguis and S. epidermidis. This influence of IL-1 on
the species- and strain-dependent induction of EC TFA suggests that
bacterial factors as well as host factors orchestrate the induction of
coagulation in an early stage in the pathogenesis of endovascular
disease, such as BE.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Bacterial Species- and Strain-Dependent Induction
of Tissue Factor in Human Vascular Endothelial Cells
*
Corresponding author. Mailing address: Department of
Infectious Diseases, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. Phone: 31-71-5261784 or 31-71-5262613. Fax: 31-71-5266758. E-mail:
beekhuiz{at}stad.dsl.nl.
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