Enzymatic oxidation of polyamines. Relationship to immunosuppressive properties

A method for the detection of spermine oxidase activity was developed using the amino acid analyzer to follow the changes in composition of incubation mixture of spermine or spermidine. Spermine oxidase activity could be detected in fetal calf serum (FCS), and six major spermine oxidation products were revealed in the incubation mixture. Incubation of spermine or spermidine with FCS produced oxidation products which suppressed lipopolysaccharide-induced mitogenesis and the murine mixed lymphocyte reaction. Oxidation was inhibited by the spermine oxidase inhibitors hydroxylamine and isonicotinic acid hydrazide, and inhibition of the immune response was no longer evident suggesting that the inhibitory material was a product of the action of the enzyme on spermic and spermidine. When FCS was used as the source of the spermine oxidase, some suppression via a cytotoxic effect could not be excluded. Mouse amniotic fluid was found to contain high levels of a spermine oxidase having a somewhat different specificity than that in FCS, and this enzyme produced a noncytotoxic immune inhibitor from cadaverine, spermidine and spermine. These data raise questions concerning the role polyamine oxidation products may play in the immunosuppression associated with pregnancy and in the generation of nonantigen-specific suppressors by cells cultured in FCS or other media containing polyamine oxidase activity.