Effects of pH on killing of Staphylococcus aureus and Escherichia coli by constituents of the neutrophil phagolysosome.
Lysosomotropic weak bases impair in-vitro neutrophil functions including intracellular killing of Staphylococcus aureus 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 H2O2 as a source of toxic oxygen metabolites. The lysosomal extract alone killed Escherichia coli strain S15 efficiently at pH 5.5 and 7.0, but had little activity against S. aureus 502a. Sublethal concentrations of the two agents, when combined, acted synergically against either organism. Each organism was killed more effectively at pH 5.5 than at pH 7.0 by the lysosome extract-H2O2 combination, but the killing of E. coli was more rapid than that of S. aureus 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 pH, and that persistence of E. coli in similar conditions does not occur because the latter is killed by lysosomal constituents in a non-pH-dependent fashion.
Styrt
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Department of Medicine, Tufts University School of Medicine, Boston, MA 02111.
Klempner
M S
MS
D000328:Adult; D000643:Ammonium Chloride / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology*
D000643:Ammonium Chloride; D006861:Hydrogen Peroxide