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In vivo suppression of allograft rejection by cyclic AMP increasing agents
This study was undertaken to elucidate the possibilities of modulating the survival of allogeneic tissue grafts by administration of cyclic AMP-increasing agents to the graft recipients. Heterotopic grafting of split mouse hearts across a strong H-2 barrier was used. It was found that Vibrio cholerae enterotoxin, which activates adenylate cyclase in mammalian cells, gave a marked prolongation of the graft survival time when given shortly before (but not after) transplantation. Also the administration of a combination of cyclic AMP and theophylline prior to or around transplantation increased graft survival time significantly. In contrast, no effect was obtained with choleragenoid, a membrane-binding cholera toxin analogue devoid of cyclic AMP-increasing activity.
This study was undertaken to elucidate the possibilities of modulating the survival of allogeneic tissue grafts by administration of cyclic AMP-increasing agents to the graft recipients. Heterotopic grafting of split mouse hearts across a strong H-2 barrier was used. It was found that Vibrio cholerae enterotoxin, which activates adenylate cyclase in mammalian cells, gave a marked prolongation of the graft survival time when given shortly before (but not after) transplantation. Also the administration of a combination of cyclic AMP and theophylline prior to or around transplantation increased graft survival time significantly. In contrast, no effect was obtained with choleragenoid, a membrane-binding cholera toxin analogue devoid of cyclic AMP-increasing activity.