Effects of cholera toxin on in vitro models of immediate and delayed hypersensitivity. Further evidence for the role of cyclic adenosine 3',5'-monophosphate.
Cholera enterotoxin inhibits the antigen-induced. IgE-mediated release of histamine from human leukocytes and the lysis of allogeneic mastocytoma cells by splenic lymphocytes from specifically immunized mice. This effect requires a prolonged preincubation time of the toxin with the lymphocyte/leukocyte preparations: a demonstrable inhibition requires about 30 min of pre-incubation and the toxin activity is still increasing at 90-180 min. Cholera enterotoxin also stimulates adenyl cyclase and leads to increased levels of cyclic AMP in the lymphocyte/leukocyte preparations. The concentration of toxin required for both cyclic AMP accumulation and inhibition of the biologic responses is about the same (ca. 1 ng/ml), and the time course of cyclic AMP accumulation parallels the development of inhibitory activity. Both activities, inhibition of the in vitro hypersensitivity reactions and cyclic AMP accumulation, are blocked by cholera antitoxin and by a toxoid prepared from the toxin (choleragenoid). These are specific antagonists in that they do not block the inhibiting activity or rise in cyclic AMP levels caused by other adenyl cyclase stimulators. Because cholera enterotoxin has no known activity other than the stimulation of adenyl cyclase and because of its unusual time course and the availability of specific antagonists, this data considerably strengthens the hypothesis that the cyclic AMP system influences the expression of these two forms of hypersensitivity phenomena.
D000818:Animals; D000992:Antitoxins / Q000494:pharmacology; D002771:Cholera; D002859:Chromium Isotopes; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D004285:Dogs; D004768:Enterotoxins / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006968:Hypersensitivity, Delayed; D006969:Hypersensitivity, Immediate; D007106:Immune Sera / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects; D013997:Time Factors
D000992:Antitoxins; D002859:Chromium Isotopes; D004768:Enterotoxins; D007106:Immune Sera; D000242:Cyclic AMP