Dual role of phagocytic NADPH oxidase in bacterial killing.
The classical model of bacterial killing by phagocytic cells has been recently challenged by questioning the toxic effect of oxygen products and attributing the fundamental role to K(+) ions in releasing antimicrobial proteins within the phagosome. In the present study we followed O(2)(*-) production, changes of membrane potential, K(+) efflux, and bacterial killing in the presence of increasing concentrations of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. Efficiency of bacterial killing was assessed on the basis of bacterial survival measured by a new semiautomated method. Very low rates of O(2)(*-) production were accompanied by significant membrane depolarization and K(+) release and parallel improvement of bacterial killing. When O(2)(*-) production exceeded 20% of its maximal capacity, no further change was detected in the membrane potential and only minimal further K(+) efflux occurred, yet bacterial survival decreased parallel to the increase of O(2)(*-) production. The presented results indicate that both electrophysiological changes (depolarization and consequent ion movements) and the chemical effect of reactive oxygen species play a significant role in the killing of certain pathogens. The observation that an increase of membrane depolarization can compensate for decreased O(2)(*-) production may be important for potential therapeutic applications.
Rada
Balázs K
BK
Department of Physiology, Semmelweis University, H-1444 Budapest, PO Box 259, Hungary.
Geiszt
Miklós
M
Káldi
Krisztina
K
Timár
Csaba
C
Ligeti
Erzsébet
E
D001419:Bacteria / Q000276:immunology*; D002478:Cells, Cultured; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D008564:Membrane Potentials; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D010587:Phagocytosis; D011188:Potassium / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013481:Superoxides; D019255:NADPH Oxidases; D015032:Zinc; D011188:Potassium