Journal of Leukocyte Biology, Vol 57, Issue 2 275-281, Copyright © 1995 by Society for Leukocyte Biology
JOURNAL ARTICLE |
A Bidani and TA Heming
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0561.
Resident alveolar macrophages (m phi) possess plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase) that plays a crucial role in regulation of intracellular pH (pHi). To assess the importance of this V-ATPase to m phi effector functions, resident alveolar m phi from rabbits were activated with E. coli-derived lipopolysaccharide (LPS) and exposed to bafilomycin A1, a specific inhibitor of V-ATPase. Bafilomycin caused a significant cytosolic acidification in both the absence and presence of CO2-HCO3-, and in both unstimulated and activated m phi. Superoxide production and Fc receptor-mediated phagocytosis also were reduced in bafilomycin-treated m phi. Similar effects were elicited by acidifying the cytoplasm in the absence of bafilomycin, by lowering extracellular pH (pHo) from 7.4 to 6.5-6.6. Thus, the effects of bafilomycin on phagocytosis and superoxide production probably were related to cytosolic acidification, secondary to blockade of V-ATPase-mediated H+ extrusion across the plasma membrane. Conversely, bafilomycin significantly increased TNF-alpha release. This effect cannot be explained by a bafilomycin-induced acidosis because acidic pHo significantly reduced TNF-alpha release. The results demonstrate that V-ATPase activity is an important determinant of the effector functions of LPS-activated m phi.
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