Proton (equivalents) are primary participants in the control and potency of the NADPH oxidase. Both the cytosolic and intraphagosomal pH are influenced during oxidase activation, and maintenance of the optimal environment requires the coordinated action of a series of sophisticated, highly regulated H(+) transporters, including the Na(+)/H(+) exchange, vacuolar H(+)-ATPase, and H(+)-conductive pathway(s). In addition, protons that are produced during some of the NADPH oxidase reactions then are substrates for the dismutation of superoxide, which precedes production of additional bactericidal agents. In this review, pH homeostasis is shown in conjunction with the NADPH oxidase to present an integrated picture of leukocyte physiology during the phagocytic response.
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