Abstract
Substantial evidence indicates that voltage-gated proton channels are activated during the phagocyte respiratory burst, when NADPH oxidase produces superoxide, a precursor to many reactive oxygen species (ROS). Originally, Henderson and colleagues (Biochem. J. 246:325-329) proposed that the function of proton extrusion was to compensate the charge translocated by the electrogenic extrusion of electrons by NADPH oxidase. (1) We believe that charge compensation remains an important function of proton current. However, proton current during the respiratory burst has additional useful consequences that could not be accomplished if the charge were compensated by other ions. (2) Proton movement from cytoplasm into the phagosome prevents large pH changes in either compartment. (3) Proton flux into the phagosome prevents excessive phagosome swelling that would occur if charge compensation were mediated by other ions. (4) Protons are required in the phagosome as substrates to produce enormous quantities of H2O2 (the immediate dismutation product of superoxide anion) as well as HOCl (believed to be a key bactericidal ROS). Quantitative estimates and modeling of events during the respiratory burst in human neutrophils and eosinophils suggest that proton current compensates at least 90-95% of the charge translocated by NADPH oxidase. Only proton current can perform all four required tasks. Supported by the Heart, Lung and Blood Institute of the NIH (HL61437). [J Physiol Sci. 2007;57 Suppl:S50]
