Staphylococcal enterotoxin B induces hepatic injury and lethal shock in endotoxin-resistant C3H/HeJ mice despite a deficient macrophage response.
Bacterial toxins, including endotoxin/LPS as well as superantigens, are major causative agents of multi-organ failure associated with sepsis and liver disease. However, the precise mechanisms initiating cell activation by the toxins have not been clarified. We compared lethal shock and cytokine production in response to LPS with responses to the superantigen staphylococcal enterotoxin B (SEB) in both LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice treated with D-galactosamine (GalN). LPS was not lethal and did not induce production of TNF-alpha in C3H/HeJ mice. In contrast, SEB produced lethal shock associated with liver failure and induced cytokines such as TNF-alpha, IFN-gamma, and IL-2 in both C3H/HeN and C3H/HeJ mice. Peritoneal macrophages from C3H/HeJ mice did not produce TNF-alpha in vitro in response to SEB or LPS. However, no significant difference was observed in production of TNF-alpha in response to stimulation in vitro by SEB between C3H/HeN and C3H/HeJ splenic lymphocytes. We have demonstrated that SEB causes lethal toxicity associated with liver injury in LPS-hyporesponsive C3H/HeJ mice and that as the underlying mechanism, the normal T-cell function in these mice still maintained the sensitivity to SEB since the genetic defect of C3H/HeJ mice unresponsive to LPS and SEB is restricted in macrophages/monocytes and does not extend to T cells.
Yasuda
Shigeo
S
First Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Nagaki
Masahito
M
Moriwaki
Hisataka
H
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000276:immunology; D005688:Galactosamine / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D008099:Liver / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012769:Shock / Q000209:etiology* / Q000401:mortality; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000633:toxicity*; D015996:Survival Rate
D016207:Cytokines; D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D005688:Galactosamine