INVITRO AND INVIVO UPTAKE OF AZITHROMYCIN (CP-62,993) BY PHAGOCYTIC-CELLS - POSSIBLE MECHANISM OF DELIVERY AND RELEASE AT SITES OF INFECTION
INVITRO AND INVIVO UPTAKE OF AZITHROMYCIN (CP-62,993) BY PHAGOCYTIC-CELLS - POSSIBLE MECHANISM OF DELIVERY AND RELEASE AT SITES OF INFECTION
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DOI：
10.1128/aac.33.3.277
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发表时间：
1989-03-01
影响因子：
4.9
通讯作者：
NEWBORG, MF
中科院分区：
文献类型：
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作者：
GLADUE, RP;BRIGHT, GM;NEWBORG, MF
阿奇霉素是一种新型氮杂内酯类抗生素，在人和小鼠多形核白细胞（PMN）、小鼠腹腔巨噬细胞以及小鼠和大鼠肺泡巨噬细胞中富集，在体外达到细胞内浓度高达外部浓度的226倍。在小鼠腹腔巨噬细胞中，阿奇霉素达到的浓度梯度（内部到外部）比红霉素高26倍。阿奇霉素的细胞摄取依赖于温度，活力和pH值，并减少2，4-二硝基苯酚。阿奇霉素不降低吞噬细胞介导的杀菌活性或影响PMN或巨噬细胞氧化爆发活性（分别为H2 O2释放或硝基蓝四唑还原）。阿奇霉素仍然在细胞内几个小时，即使在细胞外药物被删除。然而，其释放显着增强金黄色葡萄球菌的吞噬作用（82%对23%，1.5小时）。在体内，在以50 mg/kg的剂量口服治疗后20小时，在小鼠的腹膜液中发现0.05 μ g阿奇霉素。在酪蛋白酸盐诱导的PMN浸润后，腹膜腔阿奇霉素增加6倍至0.32 μ g，其中大部分是细胞内的。因此，这些细胞对阿奇霉素的摄取、转运和随后的释放表明吞噬细胞可以将活性药物递送到感染部位。
Azithromycin, a novel azalide antibiotic, concentrated in human and mouse polymorphonuclear leukocytes (PMNs),murine peritoneal macrophages, and mouse and rat alveolar macrophages, attaining intracellular concentrations up to 226 times the external concentration in vitro. In murine peritoneal macrophages, azithromycin achieved concentration gradients (internal to external) up to 26 times higher than erythromycin. The cellular uptake of azithromycin was dependent on temperature, viability, and pH and was decreased by 2,4-dinitrophenol. Azithromycin did not decrease phagocyte-mediated bactericidal activity or affect PMN or macrophage oxidative burst activity (H2O2 release or Nitro Blue Tetrazolium reduction, respectively). Azithromycin remained in cells for several hours, even after extracellular drug was removed. However, its release was significantly enhanced by phagocytosis of Staphylococcus aureus (82 versus 23% by 1.5 h). In vivo, 0.05 .mu.g of azithromycin was found in peritoneal fluids of mice 20 h after oral treatment with a dose of 50 mg/kg. Following caseinate-induced PMN infiltration, there was a sixfold increase in peritoneal cavity azithromycin to 0.32 .mu.g, most of which was intracellular. Therefore, the uptake, transport, and later release of azithromycin by these cells demonstrate that phagocytes may deliver active drug to sites of infection.