The gp91phox Component of NADPH Oxidase Is Not the Voltage-gated Proton Channel in Phagocytes, but It Helps

Thomas E. DeCoursey*, Vladimir V. Cherny, Deri Morgan, Ben Z. Katz, Mary C. Dinauer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

During the "respiratory burst," the NADPH oxidase complex of phagocytes produces reactive oxygen species that kill bacteria and other invaders (Babior, B. M. (1999) Blood 93, 1464-1476). Electron efflux through NADPH oxidase is electrogenic (Henderson, L. M., Chappell, J. B., and Jones, O. T. G. (1987) Biochem. J. 246, 325-329) and is compensated by H+ efflux through proton channels that reportedly are contained within the gp91phox subunit of NADPH oxidase. To test whether gp91 phox functions as a proton channel, we studied H+ currents in granulocytes from X-linked chronic granulomatous disease patients lacking gp91phox (X-CGD), the human myelocytic PLB-985 cell line, PLB-985 cells in which gp91phox was knocked out by gene targeting (PLBKO), and PLB-985 knockout cells re-transfected with gp91 phox (PLB91). H+ currents in unstimulated PLBKO cells had amplitude and gating kinetics similar to PLB 91 cells. Furthermore, stimulation with the phorbol ester phorbol 12-myristate 13-acetate increased H+ currents to a similar extent in X-CGD, PLBKO, and PLB91 cells. Thus, gp91phox is not the proton channel in unstimulated phagocytes and does not directly mediate the increase of proton conductance during the respiratory burst. Changes in H+ channel gating kinetics during NADPH oxidase activity are likely crucial to the activation of H+ flux during the respiratory burst.

Original languageEnglish (US)
Pages (from-to)36063-36066
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number39
DOIs
StatePublished - Sep 28 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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