Induction of acute inflammation in vivo by staphylococcal superantigens. II. Critical role for chemokines, ICAM-1, and TNF-alpha.
Superantigens such as staphylococcal enterotoxin A and B (SEA and SEB) activate the immune system by stimulating a large proportion of T lymphocytes through specific Vbeta regions of the TCR and activating macrophages by binding to MHC class II molecules. While the mechanisms by which superantigens activate T lymphocytes have been elucidated, their role in the generation of local immune responses to bacterial invasion is still unclear. In this study we have examined the ability of the superantigens SEA and SEB to elicit an inflammatory reaction in vivo, in s.c. air pouches in the mouse. Upon injection into the s.c. air pouch, the two superantigens stimulated a time-dependent increase in the number of leukocytes appearing in the pouch exudate. The leukocytes migrating into the pouch exudate were predominantly neutrophils, with some mononuclear phagocytes and eosinophils present. No T lymphocytes were detected either in the pouch lining tissue or in the exudate cells. Injection of SEA resulted in increased ICAM-1 expression, as detected by immunohistochemistry, on endothelial cells in the tissue surrounding the air pouch and accumulation of TNF-alpha and the chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1alpha, and JE in the pouch exudate. In addition, pretreatment of mice with Abs raised against ICAM-1, TNF-alpha, MIP-2, MIP-1alpha, KC, or JE inhibited leukocyte accumulation induced by SEA. These data demonstrate that bacterial superantigens may promote inflammation at extravascular sites in vivo, and that this response is secondary to the generation of inflammatory mediators, including chemokines.
Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Quebec, Canada.
P A
PA
Tessier
P H
PH
Naccache
K R
KR
Diener
R P
RP
Gladue
K S
KS
Neote
I
I
Clark-Lewis
S R
SR
McColl
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000502:physiology*; D004768:Enterotoxins / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000276:immunology* / Q000473:pathology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000008:administration & dosage* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D018925:Chemokines; D004768:Enterotoxins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal