Reaction products of 1-naphthol with reactive oxygen species prevent NADPH oxidase activation in activated human neutrophils, but leave phagocytosis intact.
Activation of human neutrophils with opsonized particles in the presence of a nontoxic dose of 1-naphthol resulted in inhibition of superoxide anion production but not of the phagocytotic activity of the cells. In this study we have investigated the mechanism of action of 1-naphthol. The inhibition is not at the level of cellular activation since the FMLP-induced rise of intracellular free calcium was unaffected. Our results show that the (metabolic) activation of 1-naphthol to 1,4-naphthoquinone by reaction with H2O2 from the oxidative burst is a necessary event for the inhibition to occur. The study provides evidence that by its reactivity with essential thiol groups 1,4-naphthoquinone (1,4-NQ) prevents the assembly of a functional NADPH-oxidase in the neutrophil membrane.
Hart
B A
BA
Department of Pharmacognosy, University of Utrecht, The Netherlands.
Simons
J M
JM
Rijkers
G T
GT
Hoogvliet
J C
JC
Van Dijk
H
H
Labadie
R P
RP
D004563:Electrochemistry; D004789:Enzyme Activation / Q000187:drug effects; D005470:Fluorometry; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019255:NADPH Oxidases; D009284:Naphthols / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology
D005609:Free Radicals; D009284:Naphthols; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010100:Oxygen