title: Superantigens from Staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL-1 beta.
abstract: BACKGROUND
  Staphylococcus aureus is one of the most common bacteria in human sepsis, a condition in which the activation of blood coagulation plays a critical pathophysiological role. During severe sepsis and septic shock microthrombi and multiorgan dysfunction are observed as a result of bacterial interference with the host defense and coagulation systems.
  
  
  OBJECTIVE
  In the present study, staphylococcal superantigens were tested for their ability to induce procoagulant activity and tissue factor (TF) expression in human whole blood and in peripheral blood mononuclear cells.
  
  
  RESULTS
  Determination of clotting time showed that enterotoxin A, B and toxic shock syndrome toxin 1 from S. aureus induce procoagulant activity in whole blood and in mononuclear cells. The procoagulant activity was dependent on the expression of TF in monocytes since antibodies to TF inhibited the effect of the toxins and TF was detected on the surface of monocytes by flow cytometry. In the supernatants from staphylococcal toxin-stimulated mononuclear cells, interleukin (IL)-1 beta was detected by ELISA. Furthermore, the increased procoagulant activity and TF expression in monocytes induced by the staphylococcal toxins were inhibited in the presence of IL-1 receptor antagonist, a natural inhibitor of IL-1 beta.
  
  
  CONCLUSIONS
  The present study shows that superantigens from S. aureus activate the extrinsic coagulation pathway by inducing expression of TF in monocytes, and that the expression is mainly triggered by superantigen-induced IL-1 beta release.
authors.affiliation: Department of Medical Microbiology, Dermatology, and Infection, Lund University Hospital, Lund, Sweden. eva.mattsson@wanadoo.nl
authors.forename: E
authors.initials: E
authors.lastname: Mattsson
authors.forename: H
authors.initials: H
authors.lastname: Herwald
authors.forename: A
authors.initials: A
authors.lastname: Egesten
mesh_terms: D001427:Bacterial Toxins; D001769:Blood; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear; D009000:Monocytes / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology*; D013925:Thromboplastin / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D013925:Thromboplastin