Role of phagocytosis in activation of the coagulation system in Streptococcus sanguis endocarditis

Abstract

The formation of vegetations consisting of fibrin, cellular elements, humoral factors, and bacteria is the central event in the pathogenesis of bacterial endocarditis. Fibrin formation occurs on the vegetation, the coagulation system being activated locally via the expression of tissue factor (TF) on fibrin-adherent monocytes. This study was performed to assess the importance of phagocytosis of fibrin-adherent Streptococcus sanguis in the stimulation of TF expression on fibrin-adherent monocytes, as well as a role for "frustrated" phagocytosis. With the latter process, these cells are unable to remove bacteria from the fibrin surface but nonetheless might be activated to generate TF. We found that serum was not required for the stimulation of TF expression by fibrin-adherent monocytes in the presence of S. sanguis in an in vitro model for bacterial endocarditis. The bacterial adhesin dextran did not influence the TF activity (TFA) of fibrin-adherent monocytes: TFA was the same after stimulation with a dextran-positive streptococcus as with its dextran-negative mutant. Furthermore, dextran did not influence the TFA of endocardial vegetations, which was the same for vegetations isolated from rabbits infected either with dextran-positive S. sanguis or its dextran-negative mutant. These results do not support the hypothesis that in bacterial endocarditis (frustrated) phagocytosis significantly contributes to TF expression on vegetation-adherent monocytes. Fibronectin, however, although not influencing the fibrin binding of the streptococci, did enhance the TFA of monocytes in a concentration-dependent manner. We conclude that although streptococci do enhance expression of TFA on monocytes, phagocytosis and bacterial adhesins do not play a major role in this process. Stimulation of monocyte TFA may be more dependent on interactions between monocytes and the vegetational surface via fibronectin receptors, such as VLA 4 and VLA 5 (very late antigens 4 and 5).