Monocytes augment bacterial species- and strain-dependent induction of tissue factor activity in bacterium-infected human vascular endothelial cells

In bacterial endocarditis (BE), intravascular infection with Staphylococcus aureus, Staphylococcus sanguis, or Staphylococcus epidermidis can lead to formation of a fibrin clot on the inner surface of the heart and cause hear t dysfunction, The events that start the coagulation in the early stage of the disease are largely unknown. We have recently shown that human endothel ial cells (EC) upon binding and internalization of S. aureus, but not S. sa nguis or S, epidermidis, express tissue factor (TF)-dependent procoagulant activity (TFA). The present study shows that infection of EC with these thr ee pathogens induces surface expression of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and monocyte adhe sion. Subsequent coculture of these cells synergistically enhanced TFA, whi ch was exclusively dependent on TF. molecules that were expressed on EC dur ing coculture, TFA induction required direct contact between monocytes and bacterium infected EC, but the signals for this response were not generated by the binding of monocytes through their beta (2)- or alpha (4)-integrins to ICAM-1 or VCAM-1, respectively, on infected EC, The mechanism by which monocytes induce TFA in bacterium-infected EC was partly mediated by the pr oinflammatory cytokine interleukin-l produced by tile cells during cocultur e, Endogenous tumor necrosis factor alpha was not involved. This modulating effect of monocytes on species- and strain-dependent TFA of bacterium-infe cted EC supports our hypothesis that in an early stage in the pathogenesis of BE! as well as other intravascular infections that lead to detrimental f ibrin formation, the coagulation cascade can be activated on the surfaces o f EC as a consequence of specific interactions between pathogenic bacteria, EC, and monocytes.