ABSTRACT This article reviews the physiology of V-type H +- translocating ATPase (V-ATPase) in light of recent findings that the electrogenic H + pump is expressed in the plasma membrane of alveolar macrophages (m ø). The plasmalemmal pump plays a determinant role in regulation of the cytosolic pH (pH i) of alveolar m ø. Selective inhibition of V-ATPase with the macrolide antibiotic bafilomycin A 1 leads to collapse of the plasma membrane electrochemical H + gradient and causes cytosolic acidosis. Treatment with bafilomycin A 1 also impairs the antimicrobial and defense functions of the m ø, depressing phagocytosis and intracellular killing of bacteria and reducing the stimulus-induced production of reactive oxygen species and tumor necrosis factor- α (a proinflammatory cytokine). Bafilomycin’s actions on these effector functions correlate with the drug-induced changes in pH i. The plasmalemmal V-ATPase probably serves to protect pH-sensitive cell functions from potentially deleterious effects of the acidic microenvironments common to sites of infection and from increases in metabolic acid production during m ø activation.
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