A study of the passive cellular transfer of local cutaneous hypersensitivity. I. Passive transfer of delayed hypersensitivity in inbred and outbred guinea-pigs.
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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.
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Effects of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complete-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction.
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