Cytokine production by murine cells activated by erythrogenic toxin type A superantigen of Streptococcus pyogenes.
The mode of pathogenic action of the Steptococcus pyogenes superantigen erythrogenic toxin type A (ETA) in causing toxic shock-like syndrome in humans is thought to be mediated by massive release of cytokines by patients immune cells. The cytokine-inducing capacity of ETA as an extracellular protein was compared with that of lipopolysaccharide (LPS), a component of cell wall of gram-negative bacteria. Peritoneal macrophages and splenocytes of BALB/c and C3H/HeJ mice were stimulated by ETA and LPS. Tumor necrosis factor (TNF), interleukin 3 (IL-3) and interleukin 6 (IL-6) activities in the supernatants of stimulated cells were evaluated. In contrast to LPS, ETA induced only low amounts of IL-6 and no detectable TNF activities in peritoneal macrophage supernatants. ETA-triggered BALB/c and C3H/HeJ splenocytes produced great amounts of IL-6. ETA triggered the production of IL-3 by both mice strains splenocytes in a dose dependent manner. The amounts of IL-3 in supernatants were comparable to those induced by concanavalin A. The simultaneous presence of ETA and LPS in macrophage and splenocyte cultures induced a slight enhancement above an additive value after 72-96 h. Challenge of BALB/c mice with ETA 6 h before the harvest of peritoneal macrophages led to an enhanced production of IL-6 upon stimulation with ETA as well as with LPS. Splenocytes of nude BALB/c mice did not produce IL-6 upon stimulation with ETA, whereas LPS-induced IL-6 production was similar in these mice and in their littermates. The pathogenic effect of ETA on host's immune cells could most likely be explained as a consequence of T cell activation. The results confirm also that LPS- and ETA-induced shock is mediated by different cell types.
Müller-Alouf
H
H
Unité des Toxines Microbiennes (URA 557 du CNRS), Paris, France.
Alouf
J E
JE
Gerlach
D
D
Fitting
C
C
Cavaillon
J M
JM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins; D016207:Cytokines / Q000096:biosynthesis*; D005098:Exotoxins / Q000276:immunology*; D007377:Interleukin-3 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008809:Mice, Inbred C3H / Q000276:immunology; D008819:Mice, Nude / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D005098:Exotoxins; D007377:Interleukin-3; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C117980:SpeA protein, Streptococcus pyogenes; D014409:Tumor Necrosis Factor-alpha; C027951:erythrogenic toxin