title: M type 1 and 3 group A streptococci stimulate tissue factor-mediated procoagulant activity in human monocytes and endothelial cells.
abstract: 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.
authors.affiliation: Veterans Affairs Medical Center, 500 West Fort Street, Building 45, Boise, Idaho 83702, USA. abryant@mindspring.com
authors.forename: A E
authors.initials: AE
authors.lastname: Bryant
authors.forename: S M
authors.initials: SM
authors.lastname: Hayes-Schroer
authors.forename: D L
authors.initials: DL
authors.lastname: Stevens
mesh_terms: D015373:Bacterial Typing Techniques; D001777:Blood Coagulation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D007249:Inflammation; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D012772:Shock, Septic / Q000097:blood / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D013290:Streptococcal Infections / Q000097:blood / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D013297:Streptococcus pyogenes / Q000145:classification* / Q000472:pathogenicity*; D013925:Thromboplastin / Q000096:biosynthesis*; D014471:Umbilical Veins
chemical_list: D016207:Cytokines; D013925:Thromboplastin