Inhibition by spermine of the induction of nitric oxide synthase in J774.2 macrophages: requirement of a serum factor

Abstract

Polyamines are endogenous regulators of various cell functions. Nitric oxide (NO) is a cytostatic and cytotoxic free radical which is produced by the inducible NO synthase (iNOS) in immuno-stimulated macrophages. We tested whether spermine modulates the induction of iNOS in J774.2 macrophages. Stimulation of macrophages by bacterial lipopolysaccharide (LPS) or gamma-interferon increased the accumulation of nitrite in the culture medium. Spermine (10(-6) - 10(-4) M) inhibited nitrite production without causing cytotoxicity. This inhibition of NO formation by spermine was significantly reduced when it was given 6 h after LPS. Spermine did not inhibit nitrite accumulation when foetal calf serum was omitted from the tissue culture medium. Thus, spermine is an inhibitor of the induction of iNOS, and its inhibitory activity requires the presence of a serum factor.