Klempner M S, Styrt B
J Antimicrob Chemother. 1983 Oct;12 Suppl C:39-50. doi: 10.1093/jac/12.suppl_c.39.
Clindamycin is concentrated within human neutrophils and their lysosomes because the intralysosomal pH is highly acidic and this antibiotic behaves as a weak base. We have examined the ability of clindamycin to buffer (alkalinize) the intralysosomal pH and studied the consequences of alterations of lysosomal pH on neutrophil functions. At therapeutic concentrations of clindamycin (0.01 mM), we observed no effect on intralysosomal pH as monitored by the distribution and fluorescence of a weakly basic fluorescent probe 9-aminoacridine. However, at higher concentrations (1.0 mM), clindamycin alkalinized the intralysosomal pH and inhibited neutrophil lysosomal degranulation to several stimuli, and superoxide production in response to phorbol myristate acetate. Neutrophil locomotion was unaffected even at concentrations of clindamycin which increased the intralysosomal pH. We conclude that clindamycin accumulates in acidic neutrophil lysosomes and, at high concentrations, alkalinizes the intralysosomal pH. Coincident with lysosomal alkalinization there is inhibition of secretion and respiratory burst activity suggesting that intact lysosomal pH regulation is important for these functions. Clindamycin provides a useful tool to examine the relationships between weak base uptake, lysosomal pH and neutrophil functions.
克林霉素在人类中性粒细胞及其溶酶体内聚集，因为溶酶体内的pH值呈强酸性，且这种抗生素表现为弱碱。我们研究了克林霉素缓冲（碱化）溶酶体内pH值的能力，并探讨了溶酶体pH值改变对中性粒细胞功能的影响。在克林霉素的治疗浓度（0.01 mM）下，通过弱碱性荧光探针9-氨基吖啶的分布和荧光监测，我们未观察到对溶酶体内pH值有影响。然而，在较高浓度（1.0 mM）时，克林霉素使溶酶体内pH值碱化，并抑制中性粒细胞溶酶体对多种刺激的脱颗粒作用，以及对佛波酯肉豆蔻酸酯乙酸盐的超氧化物生成。即使在使溶酶体内pH值升高的克林霉素浓度下，中性粒细胞的运动也未受影响。我们得出结论，克林霉素在酸性中性粒细胞溶酶体中积累，且在高浓度时使溶酶体内pH值碱化。与溶酶体碱化同时发生的是分泌和呼吸爆发活性受到抑制，这表明完整的溶酶体pH调节对这些功能很重要。克林霉素为研究弱碱摄取、溶酶体pH值与中性粒细胞功能之间的关系提供了一个有用的工具。
