Consequences of the electrogenic function of the phagocytic NADPH oxidase.
NADPH oxidase of phagocytic cells transfers a single electron from intracellular NADPH to extracellular O2, producing superoxide (O.-2), the precursor to several other reactive oxygen species. The finding that a genetic defect of the enzyme causes chronic granulomatous disease (CGD), characterized by recurrent severe bacterial infections, linked O.-2 generation to destruction of potentially pathogenic micro-organisms. In this review, we focus on the consequences of the electrogenic functioning of NADPH oxidase. We show that enzyme activity depends on the possibilities for compensating charge movements. In resting neutrophils K+ conductance dominates, but upon activation the plasma membrane rapidly depolarizes beyond the opening threshold of voltage-gated H+ channels and H+ efflux becomes the major charge compensating factor. K+ release is likely to contribute to the killing of certain bacteria but complete elimination only occurs if O.-2 production can proceed at full capacity. Finally, the reversed membrane potential of activated neutrophils inhibits Ca2+ entry, thereby preventing overloading the cells with Ca2+. Absence of this limiting mechanism in CGD cells may contribute to the pathogenesis of the disease.
Rada
Balázs K
BK
Semmelweis University Department of Physiology PO Box 259, 1444 Budapest, Hungary.
Geiszt
Miklós
M
Hably
Csilla
C
Ligeti
Erzsébet
E
D001419:Bacteria / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D004926:Escherichia coli; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D013211:Staphylococcus aureus; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D019255:NADPH Oxidases; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium; D002118:Calcium