Role of monocytes in experimental Staphylococcus aureus endocarditis

In the pathogenesis of bacterial endocarditis (BE), the clotting system pla ys a cardinal role in the formation and maintenance of the endocardial vege tations. The extrinsic pathway is involved in the activation of the coagula tion pathway with tissue factor (TF) as the key protein. Staphylococcus aur eus is a frequently isolated bacterium from patients with BE. We therefore investigated whether S. aureus can induce TF activity (TFA) on fibrin-adher ent monocytes, used as an in vitro model of BE. We also assessed in vivo in rabbits with catheter induced vegetations, the effect of S. aureus infecti on on vegetational TFA. In vitro experiments showed that adherent S. aureus induced TFA on fibrin-adherent monocytes which was optimal at a bacterium/ monocyte ratio of 1 to 1. Monocyte damage occurred when this ratio exceeded 4 to 1 (visually) or 6 to 1 (propidium iodide influx) Consequently, TFA de creased. In vivo S. aureus led to very high bacterial numbers in the vegeta tions and a significant increase of their weight. However, TFA of infected vegetations was the same as of sterile ones. This may be due to the high ba cteria to monocyte ratio as well as bacterium-induced monocyte damage. Teic oplanin treatment of infected rabbits reduced bacterial numbers in the bloo d and in the vegetations. Two-day treatment resulted in an increase of vege tational TFA, but after four-day treatment vegetational TFA dropped, most p robably due to a suboptimal bacterium/monocyte ratio. S. aureus endocarditi s in etoposide (Vepesid)-treated rabbits, leading to a selective monocytope nia, caused a rapid death of the animals. In these rabbits no vegetations w ere found at all. We conclude that, like Streptococcus sanguis and Staphylo coccus epidermidis, S. aureus is able to induce TFA in fibrin-adherent bloo d monocytes. In addition, monocytes have a protective effect during the cou rse of S. aureus endocarditis.