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Infection and Immunity, April 2003, p. 1903-1910, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1903-1910.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

M Type 1 and 3 Group A Streptococci Stimulate Tissue Factor-Mediated Procoagulant Activity in Human Monocytes and Endothelial Cells

A. E. Bryant,1,2* S. M. Hayes-Schroer,1,2 and D. L. Stevens1,3

Veterans Affairs Medical Center, Boise,1 University of Idaho, Moscow, Idaho,2 University of Washington School of Medicine, Seattle, Washington3

Received 5 June 2002/ Returned for modification 31 October 2002/ Accepted 10 December 2002

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.

* Corresponding author. Mailing address: Infectious Diseases Section, Veterans Affairs Medical Center, 500 West Fort St. (Bldg. 45), Boise, ID 83702. Phone: (208) 422-1599. Fax: (208) 422-1365. E-mail: abryant{at}mindspring.com.

Editor: V. J. DiRita

Infection and Immunity, April 2003, p. 1903-1910, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1903-1910.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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