Miller M F, Martin J R, Johnson P, Ulrich J T, Rdzok E J, Billing P
J Infect Dis. 1984 May;149(5):714-8. doi: 10.1093/infdis/149.5.714.
Studies were undertaken to demonstrate the efficacy of erythromycin in killing Legionella pneumophila organisms that have been ingested by human polymorphonuclear leukocytes. With use of an electron microscope-autoradiography method in conjunction with an antibiotic-uptake assay, it was shown that [3H]-labeled erythromycin A base penetrated into the cytoplasm of human polymorphonuclear leukocytes in concentrations up to 24 times higher than the extracellular drug level. Similar studies using [14C]benzyl penicillin revealed that this antibiotic penetrated human polymorphonuclear leukocytes very poorly. Removal of erythromycin from the extracellular environment resulted in rapid leakage of radioactivity from the cells; an assay for bioactivity showed that this material was unaltered drug. Human polymorphonuclear leukocytes were permitted to ingest L. pneumophila and were then treated with erythromycin A base. The erythromycin killed the ingested legionellae, as evidenced by bacterial plate counts and morphological destruction of ingested organisms. These data clearly demonstrate the efficacy of erythromycin in killing susceptible intracellular pathogens.
开展了多项研究以证明红霉素对被人类多形核白细胞摄取的嗜肺军团菌的杀灭效果。通过将电子显微镜放射自显影方法与抗生素摄取测定相结合，结果显示，[3H]标记的红霉素A碱以高达细胞外药物水平24倍的浓度渗透到人类多形核白细胞的细胞质中。使用[14C]苄青霉素进行的类似研究表明，这种抗生素很难渗透到人类多形核白细胞中。从细胞外环境中去除红霉素会导致放射性物质从细胞中迅速泄漏；生物活性测定表明，这种物质是未改变的药物。让人类多形核白细胞摄取嗜肺军团菌，然后用红霉素A碱进行处理。如细菌平板计数和摄取的生物体的形态破坏所示，红霉素杀死了摄取的军团菌。这些数据清楚地证明了红霉素在杀灭易感细胞内病原体方面的效果。
