Protection of U937 cells from free radical damage by the macrophage synthesized antioxidant 7,8-dihydroneopterin

Interferon-gamma stimulation of human macrophages causes the synthesis and release of neopterin and its reduced form 7,8-dihydroneopterin (7,8-NP). Th e purpose of this cellular response is undetermined but in vitro experiment s suggests 7,8-NP is an antioxidant. We have found 7,8-NP can protect monoc yte-like U937 cells from oxidative damage. 7,8-NP inhibited ferrous ion and hypochlorite mediated loss of cell viability. Fe++ mediated lipid peroxida tion was effectively inhibited by 7,8-NP, however no correlation was found between peroxide concentration and cell viability. Hypochlorite was scaveng ed by 7,8-NP, preventing the loss of cell viability. 7,8-NP was less effect ive in inhibiting H2O2-mediated loss of cell viability with significant inh ibition only occurring at high 7,8-NP concentrations. Analysis of cellular protein hydrolysates showed none of the oxidants caused the formation of an y protein bound DOPA or dityrosine but did show 7,8-NP prevented the loss o f cellular tyrosine by HOCL Our data suggests macrophages may synthesize 7, 8-NP for antioxidant protection during inflammatory events in vivo.