Monocytes Augment Bacterial Species- and Strain-Dependent Induction of Tissue Factor Activity in Bacterium-Infected Human Vascular Endothelial Cells

Abstract

In bacterial endocarditis (BE), intravascular infection with Staphylococcus aureus, Streptococcus sanguis, orStaphylococcus epidermidis can lead to formation of a fibrin clot on the inner surface of the heart and cause heart dysfunction. The events that start the coagulation in the early stage of the disease are largely unknown. We have recently shown that human endothelial cells (EC) upon binding and internalization of S. aureus, but not S. sanguis or S. epidermidis, express tissue factor (TF)-dependent procoagulant activity (TFA). The present study shows that infection of EC with these three pathogens induces surface expression of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and monocyte adhesion. Subsequent coculture of these cells synergistically enhanced TFA, which was exclusively dependent on TF molecules that were expressed on EC during 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 ␤ 2 -or ␣ 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 proinflammatory cytokine interleukin-1 produced by the cells during coculture. Endogenous tumor necrosis factor alpha was not involved. This modulating effect of monocytes on species-and strain-dependent TFA of bacterium-infected EC supports our hypothesis that in an early stage in the pathogenesis of BE, as well as other intravascular infections that lead to detrimental fibrin formation, the coagulation cascade can be activated on the surfaces of EC as a consequence of specific interactions between pathogenic bacteria, EC, and monocytes.

A functional polymorphism (−603A → G) in the tissue factor gene promoter is associated with adult-onset asthma

“…Several environmental factors have been identified, such as strong inducers of TF gene expression, including viruses, 44 bacteria, [45][46][47] other microbial pathogens such as cytomegalovirus, Chlamydia pneumoniae, Streptococcus sanguis and Plasmodium falciparum, [48][49][50] endotoxin 51 and oxidative air pollutant particulate matter. 52 In this study, we showed that the G allele in the À603 position is associated with a higher promoter activity than the A allele in vitro.…”

Inflammatory Response in Infective Endocarditis

“…Exposure of the valve stromal cell to the blood induced PCA following interaction with lipopolysaccarides (LPS) and IL-l. Induction of tissue factor activity (TFA) by bacteria mainly depends on their ability to internalize within the endothelial cell (12) Bacterial colonization within the vegetation tPMP Once there is activation of the coagulation system and the inflammatory response, host defense mechanisms are activated against the invading bacteria. Activated platelets are capable of secreting thrombin that induces platelets microbiocidal peptides production (tPMP) (13).…”

Polymorphisms in the 5′‐UTR of the tissue factor gene are associated with altered expression in human endothelial cells

“…Exposure to inflammatory agents, however, quickly upregulates TF expression in these vascular cell types. Induction of TF expression on monocytes and endothelial cells has been linked to the pathology of a number of diseases [5][6][7]. In addition, TF-bearing circulating microparticles of endothelial origin may contribute to the pathology of acute coronary syndromes [8].…”