Lysosomotropic weak bases impair in-vitro neutrophil functions including intracellular killing of strain 502a. To investigate whether prevention of phagosomal acidification could account for impaired microbicidal activity, a model phagosome was formulated with a freeze-thawed granule extract as a source of lysosomal enzymes and HO as a source of toxic oxygen metabolites. The lysosomal extract alone killed strain S15 efficiently at H 5·5 and 7·0, but had little activity against 502a. Sublethal concentrations of the two agents, when combined, acted synergically against either organism. Each organism was killed more effectively at H 5·5 than at H 7·0 by the lysosome extract-HO combination, but the killing of was more rapid than that of in the same conditions. These findings suggest that impairment of neutrophil antistaphylococcal activity by weak bases may be mediated by their ability to raise phagosomal H, and that persistence of in similar conditions does not occur because the latter is killed by lysosomal constituents in a non-H-dependent fashion.


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