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Current Topics in Pharmacology   Volumes    Volume 4 
Abstract
Bafilomycin A1, a selective inhibitor of V-ATPase: influence on pH regulation and effector functions of alveolar macrophages
Thomas A. Heming, Akhil Bidani
Pages: 163 - 172
Number of pages: 10
Current Topics in Pharmacology
Volume 4 

Copyright © 1998 Research Trends. All rights reserved

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 (mø). The plasmalemmal pump plays a determinant role in regulation of the cytosolic pH (pHi) of alveolar mø. Selective inhibition of V-ATPase with the macrolide antibiotic bafilomycin A1 leads to collapse of the plasma membrane electrochemical H+ gradient and causes cytosolic acidosis. Treatment with bafilomycin A1 also impairs the antimicrobial and defense functions of the mø, 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 pHi. 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 mø activation.

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