Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst
- Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, and Department of Cardiovascular Research, Manton Center for Orphan Disease, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115
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Contributed by David E. Clapham, March 16, 2009 (received for review January 9, 2009)
Abstract
Granulocytes generate a “respiratory burst” of NADPH oxidase-dependent superoxide anion (O2−∙) production that is required for efficient clearance of bacterial pathogens. Hv1 mediates a voltage-gated H+ channel activity that is proposed to serve a charge-balancing role in granulocytic phagocytes such as neutrophils and eosinophils. Using mice in which the gene encoding Hv1 is replaced by β-Geo reporter protein sequence, we show that Hv1 expression is required for measurable voltage-gated H+ current in unstimulated phagocytes. O2−∙ production is substantially reduced in the absence of Hv1, suggesting that Hv1 contributes a majority of the charge compensation required for optimal NADPH oxidase activity. Despite significant reduction in superoxide production, Hv1−/− mice are able to clear several types of bacterial infections.
Footnotes
- 2To whom correspondence should be addressed. E-mail: dclapham{at}enders.tch.harvard.edu
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Author contributions: I.S.R. and D.E.C. designed research; I.S.R., E.R., and J.S.K. performed research; I.S.R. contributed new reagents/analytic tools; I.S.R. analyzed data; and I.S.R. and D.E.C. wrote the paper.
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↵1Present address: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, 1101 East Marshall Street, P.O. Box 980551, Richmond, VA 23298.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0902761106/DCSupplemental.
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Freely available online through the PNAS open access option.
