Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst

Granulocytes generate a respiratory burst'' of NADPH oxidase-dependent superoxide anion (O-2(-center dot)) 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 beta-Geo reporter protein sequence, we show that Hv1 expression is required for measurable voltage-gated H+ current in unstimulated phagocytes. O-2(-center dot) 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.