Styrt B, Klempner M S
Department of Medicine, Tufts University School of Medicine, Boston, MA 02111.
J Med Microbiol. 1988 Feb;25(2):101-7. doi: 10.1099/00222615-25-2-101.
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.
溶酶体亲和性弱碱会损害体外中性粒细胞功能，包括对金黄色葡萄球菌502a菌株的细胞内杀伤作用。为了研究吞噬体酸化的抑制是否可以解释杀菌活性受损的原因，构建了一个模型吞噬体，其含有冻融颗粒提取物作为溶酶体酶的来源，以及H2O2作为有毒氧代谢产物的来源。单独的溶酶体提取物在pH 5.5和7.0时能有效杀死大肠杆菌S15菌株，但对金黄色葡萄球菌502a几乎没有活性。两种药物的亚致死浓度联合使用时，对任何一种生物体都有协同作用。在pH 5.5时，溶酶体提取物-H2O2组合比在pH 7.0时更有效地杀死每种生物体，但在相同条件下，大肠杆菌的杀伤速度比金黄色葡萄球菌更快。这些发现表明，弱碱对中性粒细胞抗葡萄球菌活性的损害可能是由它们提高吞噬体pH值的能力介导的，并且在类似条件下大肠杆菌不会持续存在，因为后者以非pH依赖的方式被溶酶体成分杀死。
