Hand W L, Corwin R W, Steinberg T H, Grossman G D
Am Rev Respir Dis. 1984 Jun;129(6):933-7. doi: 10.1164/arrd.1984.129.6.933.
To provide additional criteria for therapy of pulmonary infections caused by facultative intracellular bacteria, we studied the uptake of 12 antibiotics by alveolar macrophages (AM) obtained from healthy, young volunteers by bronchoalveolar lavage. These human AM were incubated with radiolabeled antibiotics for periods as long as 2 h. Entry of antimicrobials into the cells was determined by means of a velocity-gradient centrifugation technique. Antibiotic uptake was expressed as the ratio of the cellular to the extracellular drug concentration (C/E). Penicillin G, cefamandole, and gentamicin were taken up poorly by human AM (C/E = 0.5 to 0.8). Isoniazid achieved a cellular concentration similar to the extracellular level of the drug (C/E = 0.9). Chloramphenicol, rifampin, tetracycline, and lincomycin, drugs that are lipid-soluble, were concentrated several-fold by AM (C/E = 2 to 5). The remaining antibiotics tested, clindamycin, erythromycin, erythromycin propionate, and ethambutol, were markedly concentrated by AM (C/E = 9 to 23). Accumulation of clindamycin (C/E = 23) was a rapid, active, energy-requiring process, which appeared to be dependent upon mitochondrial oxidative metabolism. The ability of the tested antimicrobial agents to enter human AM correlates well with the efficacy of these drugs in treatment of certain intracellular pulmonary infections.
为了为兼性胞内菌引起的肺部感染提供更多治疗标准，我们研究了从健康年轻志愿者通过支气管肺泡灌洗获得的肺泡巨噬细胞（AM）对12种抗生素的摄取情况。这些人AM与放射性标记的抗生素孵育长达2小时。通过速度梯度离心技术测定抗菌药物进入细胞的情况。抗生素摄取以细胞内药物浓度与细胞外药物浓度之比（C/E）表示。青霉素G、头孢孟多和庆大霉素被人AM摄取较差（C/E = 0.5至0.8）。异烟肼在细胞内达到的浓度与细胞外药物水平相似（C/E = 0.9）。氯霉素、利福平、四环素和林可霉素这些脂溶性药物被AM浓缩了几倍（C/E = 2至5）。其余测试的抗生素，克林霉素、红霉素、丙酸红霉素和乙胺丁醇，被AM显著浓缩（C/E = 9至23）。克林霉素的积累（C/E = 23）是一个快速、活跃、需要能量的过程，似乎依赖于线粒体氧化代谢。测试的抗菌剂进入人AM的能力与这些药物在治疗某些细胞内肺部感染中的疗效密切相关。
