Skin reactivity of unsensitized monkeys upon challenge with staphylococcal enterotoxin B: a new approach for investigating the site of toxin action.
The correlation between skin tests and emetic responses in unsensitized monkeys was used to elucidate the cellular site of action of staphylococcal enterotoxin B (SEB). Evidence is presented that SEB administered intradermally provoked immediate-type skin reactions associated with mild degranulation of cutaneous mast cells. The cytoplasma showed signs of synthetic and metabolic activity, with formation of vesicles and increased prominence of mitochondria. Carboxymethylation of histidine residues of SEB altered the molecule (cSEB) from more alkaline components to more acidic species with increased microheterogeneity. This modification caused a loss in toxicity and completely abrogated the skin-sensitizing activity without changing the immunological specificity. cSEB, however, could compete with SEB for binding sites on the target cell surface. Previously, compound 48/80-treated skin sites behaved refractively to challenge with SEB, indicating that mediators from cutaneous mast cells are required for SEB-induced skin reactions. Skin reactions as well as emetic responses challenged with SEB were completely inhibited by H2 receptor antagonists and calcium channel blockers but not by H1 antihistamine or competitive antagonists of serotonin. This new approach provides a model for investigating the mechanisms of SEB action.
Scheuber
P H
PH
Golecki
J R
JR
Kickhöfen
B
B
Scheel
D
D
Beck
G
G
Hammer
D K
DK
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004639:Emetics / Q000494:pharmacology; D004768:Enterotoxins / Q000633:toxicity*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008252:Macaca fascicularis; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000187:drug effects* / Q000648:ultrastructure; D012882:Skin Tests; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004639:Emetics; D004768:Enterotoxins; D006634:Histamine H1 Antagonists; C031818:enterotoxin B, staphylococcal; D003189:p-Methoxy-N-methylphenethylamine