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 human neutrophils were examined ex vivo. When neutrophils isolated from fresh blood were incubated with 6-formylpterin, the intracellular production of hydrogen peroxide (H(2)O(2)) occurred. The H(2)O(2) generation by 6-formylpterin in neutrophils occurred in the presence of diphenyleneiodonium (DPI), an inhibitor of NADPH-oxidase. When neutrophils were incubated with DPI, the killing rate of catalase-positive bacteria, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), significantly decreased. This impaired bactericidal activity of the DPI-treated neutrophils was a mimic for chronic granulomatous disease (CGD). However, the killing rate of the DPI-treated neutrophils against E. coli and S. aureus significantly increased when 6-formylpterin was administered. Since 6-formylpterin intracellularly generates H(2)O(2) independent from the NADPH-oxidase, it was considered to improve the impaired bactericidal activity of the DPI-treated neutrophils. The use of 6-formylpterin may serve as an option of therapy for CGD.
Yamashita
K
K
Department of Hematology and Oncology, Kyoto University, Kyoto 606-8507, Japan.
Arai
T
T
Fukuda
K
K
Mori
H
H
Ishii
H
H
Nishioka
M
M
Tajima
K
K
Makino
K
K
Sasada
M
M
D000328:Adult; D001770:Blood Bactericidal Activity / Q000187:drug effects* / Q000502:physiology; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D006105:Granulomatous Disease, Chronic / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D011621:Pteridines / Q000378:metabolism / Q000494:pharmacology*; D011622:Pterins; D013211:Staphylococcus aureus / Q000276:immunology
D004791:Enzyme Inhibitors; D009861:Onium Compounds; D011621:Pteridines; D011622:Pterins; C007517:diphenyleneiodonium; C005926:2-amino-4-hydroxy-6-formylpteridine; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases