The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites

摘要: 1. We have recently found that in the presence, but not absence, of foetal calf serum, spermine inhibits production nitric oxide (NO) cultured J774.2 macrophages stimulated with bacterial endotoxin (lipopolysaccharide; LPS) or gamma-interferon (IFN), showing polyamines may act as suppressants NO-mediated immune functions. Here, we studied mechanisms and specificity this inhibitory action. 2. Other polyamines, well spermine, inhibit formation NO macrophages, order potency being > spermidine >> putrescine = cadaverine. This inhibition is due to any cytotoxic effect these agents for they neither reduced mitochondrial respiration nor increased release lactate dehydrogenase into supernatant. 3. Spermine a direct inhibitor activity iNOS induced cells measured by its lack on conversion L-arginine L-citrulline homogenates. Neither metabolites, interfere nitrite from scavengers NO. Thus, an induction iNOS. 4. presence foetal, newborn adult bovine rat human serum. 5. The sper mine can be prevented isoniazid, hydrazine hydroxylamine, inhibitors oxidase, phenylhydrazine, aldehyde inhibitor. have, therefore, tested effects dialdehyde malon (SDA, 10(-5) M) IFN-activated absence serum when given pretreatment 6 h after stimulation. In contrast, was ineffective. metabolites such SDA, account NOS vitro. 6. appears fairly specific iNOS, does LPS-induced prostaglandin F2 alpha tumour necrosis factor.