Bafilomycin A1 inhibits lysosomal, phagosomal, and plasma membrane H(+)-ATPase and induces lysosomal enzyme secretion in macrophages.
Bafilomycin A1, a specific inhibitor of H(+)-ATPases of the vacuolar type, was in the present study shown, at similar concentrations, to induce secretion of lysosomal enzyme and to elevate lysosomal pH in mouse macrophages. These results lend support to the previous suggestion of a triggering role for an increase in lysosomal pH and a permissive role for cytosolic pH in the exocytosis of macrophage lysosomal enzyme. Vacuolar H(+)-ATPases are present in the macrophage plasma membrane as well as in intracellular membranes, for example, those of the lysosomal and phagosomal compartments. Phagosomal acidification was shown to be achieved in part by a mechanism with a similar sensitivity to bafilomycin A1 as lysosomal H+ transport and in part by an early, bafilomycin A1-insensitive mechanism. We found a lesser sensitivity towards bafilomycin A1 of the lysosomal and phagosomal H(+)-ATPase than that localized in the plasma membrane, indicating differences among H(+)-ATPases at the subcellular level. Also, by attempts to mobilize lysosomal H(+)-ATPase to the plasma membrane, support was obtained for the notion that subcellular H(+)-ATPase populations differ and thus possibly could be differentially regulated.
Tapper
H
H
Department of Medical and Physiological Chemistry, Lund University, Sweden.
Sundler
R
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000201:enzymology*; D018942:Macrolides; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D010588:Phagosomes / Q000201:enzymology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D018942:Macrolides; C057620:bafilomycin A; D006180:Proton-Translocating ATPases