6-formylpterin intracellularly generates hydrogen peroxide and restores the impaired bactericidal activity of human neutrophils

The effects of 6-formylpterin on the impaired bactericidal activity of huma n neutrophils were examined ex vivo. When neutrophils isolated from fresh b lood were incubated with 6-formylpterin, the intracellular production of hy drogen peroxide (H2O2) occurred. The H2O2, generation by 6-formylpterin in neutrophils occurred in the presence of diphenyleneiodonium. (DPI), an inhi bitor of NADPH-oxidase. When neutrophils were incubated with DPI, the killi ng rate of catalase-positive bacteria, Escherichia coli (E. coli) and Staph ylococcus aureus (S. aureus), significantly decreased. This impaired bacter icidal activity of the DPI-treated neutrophils was a mimic for chronic gran ulomatous disease (CGD). However, the killing rate of the DPI-treated neutr ophils against E. coli and S. aureus significantly increased when 6-formylp terin was administered. Since 6-formylpterin intracellularly generates H2O2 independent from the NADPH-oxidase, it was considered to improve the impai red bactericidal activity of the DPI-treated neutrophils. The use of 6-form ylpterin may serve as an option of therapy for CGD. (C) 2001 Academic Press .