In:
Philosophical Transactions of the Royal Society B: Biological Sciences, The Royal Society, Vol. 360, No. 1464 ( 2005-12-29), p. 2293-2300
Abstract:
NADPH oxidase of phagocytic cells transfers a single electron from intracellular NADPH to extracellular O 2 , producing superoxide , 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 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 production can proceed at full capacity. Finally, the reversed membrane potential of activated neutrophils inhibits Ca 2+ entry, thereby preventing overloading the cells with Ca 2+ . Absence of this limiting mechanism in CGD cells may contribute to the pathogenesis of the disease.
Type of Medium:
Online Resource
ISSN:
0962-8436
,
1471-2970
DOI:
10.1098/rstb.2005.1768
Language:
English
Publisher:
The Royal Society
Publication Date:
2005
detail.hit.zdb_id:
1462620-2
SSG:
12
