Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin, telithromycin, and cethromycin
Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin, telithromycin, and cethromycin
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DOI：
10.1128/aac.49.6.2372-2377.2005
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发表时间：
2005-06-01
影响因子：
4.9
通讯作者：
Parnham, MJ
中科院分区：
文献类型：
--
作者：
Bosnar, M;Kelneric, Z;Parnham, MJ
大环内酯类抗生素具有在宿主细胞，特别是吞噬细胞内集中的突出能力。本研究比较了5种不同的大环内酯类抗生素在人外周血多形核中性粒细胞（PMNs）和3种不同细胞系、2种吞噬细胞系（RAW 264.7和THP-1）和1种上皮细胞系（MDCK）中的摄取和释放动力学。根据获得的结果，测试的物质可以归为不同的组。阿奇霉素构成第一组，其特点是迅速和不饱和地被吞噬细胞吸收，并在预载细胞中高度保留。第二组包括红霉素和克拉霉素。这两种物质不表现出细胞特异性；因此，它们被吸收到相似的程度，并被研究的所有细胞类型释放。酮内酯是最后一类。它们在单核细胞谱系和髓系未分化细胞中摄取是饱和的，并且从所有研究的细胞系中迅速释放。然而，在pmn中，酮内酯的摄取是不饱和的；与特利红霉素不同的是，头孢霉素能迅速从装载的细胞中排出。
Macrolide antibiotics have an outstanding ability to concentrate within host cells, particularly phagocytes. In the study described in this paper five different macrolide antibiotics were compared regarding the uptake and release kinetics in human peripheral blood polymorphonuclear neutrophils (PMNs) and three different cell lines, two phagocytic cell lines (RAW 264.7 and THP-1) and an epithelial cell line (MDCK). Based on the results obtained, the substances tested could be clustered into different groups. Azithromycin constituted the first group, characterized by rapid and nonsaturable uptake into phagocytic cells and a high degree of retention in the preloaded cells. The second group included erythromycin and clarithromycin. These two substances do not exhibit cell specificity; consequently, they are taken up to a similar extent and are released by all cell types studied. Ketolides constituted the last group. Their uptake was saturable in cells of monocytic lineage as well as in nondifferentiated cells of myeloid lineage, and they were rapidly released from all the cell lines studied. However, in PMNs, ketolide uptake was, not saturable; and unlike telithromycin, cethromycin rapidly egressed from the loaded cells.