thromboplastin and Streptococcal-Infections

Although streptococcal and S. aureus IE share the same primary site of infection, their pathogenesis and clinical evolution present several major differences. Streptococci adhere to cardiac valves with pre-existing endothelial lesions. In contrast, S. aureus can colonize either damaged endothelium or invade physically intact endothelial cells. These interactions are mediated by multiple surface adhesins, some of which have been only partially characterized. Streptococci produce surface glucans (gtf and ftf), ECM adhesins (e.g., fibronectin-binding proteins, FimA), and platelet aggregating factors (phase I and phase II antigens, pblA, pblB, and pblT), all of which have been.

Topics: Adhesins, Bacterial; Antigens, Surface; Bacterial Proteins; Blood Platelets; Endocarditis, Bacterial; Extracellular Matrix; Heart Valves; Humans; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Thromboplastin

Streptococcal toxic shock syndrome (StrepTSS) is an invasive infection characterized by marked coagulopathy, multiple organ failure, and rapid tissue destruction and is strongly associated with M type 1 and 3 group A streptococci (GAS). Initiation of the coagulation cascade with formation of microvascular thrombi contributes to multiple organ failure in human cases of gram-negative bacteremia; however, little is known regarding the mechanism of coagulopathy in StrepTSS. Thus, we investigated the abilities of several strains of M type 1 and 3 GAS isolated from human cases of StrepTSS to stimulate production of tissue factor (TF), the principal initiator of coagulation in vivo. Washed, killed M type 1 and 3 GAS, but not M type 6 GAS, elicited high-level TF-mediated procoagulant activity from both isolated human monocytes and cultured human umbilical vein endothelial cells. M type 1 GAS consistently elicited higher levels of TF from monocytes than did M type 3 GAS. GAS-induced TF synthesis in monocytes did not correlate with production of tumor necrosis factor alpha or interleukin-8. Conversely, M type 3 GAS were consistently more potent than M type 1 GAS in stimulating endothelial cell TF synthesis. These results demonstrate that (i) M type 1 and 3 strains of GAS are potent inducers of TF synthesis, (ii) GAS-induced TF synthesis is not simply an epiphenomenon of cytokine generation, and (iii) induction of TF in endothelial cells and monocytes may be M type specific. In total, these findings suggest that a novel interaction between GAS and host cells contributes to the observed coagulopathy in StrepTSS.

Topics: Bacterial Typing Techniques; Blood Coagulation; Cells, Cultured; Cytokines; Endothelium, Vascular; Humans; Inflammation; Monocytes; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes; Thromboplastin; Umbilical Veins

A main feature in the pathogenesis of bacterial endocarditis is the activation of the coagulation system via the extrinsic pathway, resulting in the formation of infected endocardial vegetations. Earlier studies gave indirect evidence that monocytes play an important role in the procoagulant response during the course of the disease. In this study, we assessed the role of monocytes more directly. We compared weights and tissue factor activities (TFA) of endocardial vegetations of normal rabbits infected with Streptococcus sanguis with those of rabbits which were treated with the cytostatic drug etoposide (Vepesid; Bristol-Myers Squibb B.V.) to induce a selective monocytopenia. Furthermore, the importance of the presence of bacteria was determined through the influence of antibiotic treatment on TFA, vegetational weight, and infection of the vegetations. The TFA of the vegetations was measured chromogenically by monitoring the factor VII-dependent activation of factor X with an amidolytic assay for factor Xa. We found that the degree of infection and the weight of vegetations of rabbits treated with the cytostatic drug etoposide did not differ from that of untreated rabbits. Their TFA, however, was significantly lower than the TFA of vegetations of rabbits not treated with etoposide. We also found that, as with the monocytopenic rabbits, the weight of the vegetations was not reduced in penicillin G-treated rabbits. The degree of infection and TFA, however, were significantly lower. We conclude that monocytes indeed are involved in the activation of the coagulation system during the course of bacterial endocarditis and that the degree of infection is positively correlated to the TFA of the vegetations.

Topics: Animals; Endocardium; Etoposide; Integrins; Male; Monocytes; Penicillin G; Penicillins; Rabbits; Streptococcal Infections; Streptococcus sanguis; Thromboplastin

To investigate activation of the coagulation system in bacterial endocarditis, we determined the procoagulant activity of blood monocytes isolated from rabbits with Streptococcus sanguis-infected or sterile catheter-induced endocardial vegetations. This activity was determined directly after isolation from the peripheral blood and after stimulation in vitro by either endotoxin or by phagocytosis of S. sanguis. The procoagulant activity of the vegetations of these rabbits was also determined. The procoagulant activity of blood monocytes of rabbits with S. sanguis endocarditis was found to be similar to the activity of monocytes of rabbits with sterile vegetations, both at the time of isolation and after stimulation in vitro by exposure to endotoxin or phagocytosis of bacteria. The procoagulant activity of infected vegetations was significantly higher than that of sterile vegetations. We conclude that in bacterial endocarditis the coagulation system is activated locally at the site of the vegetation. Triggering probably occurs by thromboplastin generated by monocytes activated by phagocytosis of bacteria on the vegetational surface.

Topics: Animals; Blood Coagulation Factors; Endocarditis, Bacterial; Endocardium; Factor X; Male; Monocytes; Phagocytosis; Prothrombin; Rabbits; Streptococcal Infections; Streptococcus sanguis; Thromboplastin