Clarithromycin transport by gingival fibroblasts and epithelial cells
Clarithromycin transport by gingival fibroblasts and epithelial cells
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DOI：
10.1177/154405910808700812
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发表时间：
2008-08-01
影响因子：
7.6
通讯作者：
Walters, J. D.
中科院分区：
文献类型：
--
作者：
Chou, C. -H.;Walters, J. D.
大环内酯类抗生素穿透细胞，但其发生机制尚不清楚。本研究的目的是表征牙龈成纤维细胞和口腔上皮细胞摄取克拉霉素的机制。将培养的人牙龈成纤维细胞和SCC-25细胞与[H-3]-克拉霉素孵育。我们通过测量随时间推移的细胞相关放射性来测定克拉霉素转运。成纤维细胞和上皮细胞迅速积累克拉霉素，在15分钟内达到稳态细胞内浓度。在含2 μ g/mL克拉霉素的培养基中孵育，在成纤维细胞和SCC-25细胞中的稳态细胞内浓度分别为75.8 μ g/mL和6.6 μ g/mL。克拉霉素转运表现为米氏动力学，在低于37 ℃时受到抑制。对于成纤维细胞和SCC-25细胞，米氏常数分别为78.4和227 μ g/mL，而最大转运速度分别为264和381 ng/min/10（6）个细胞。因此，两种类型的细胞通过集中主动转运系统摄取克拉霉素。通过增加细胞内克拉霉素水平，该系统可增强克拉霉素对侵袭性牙周病原体的有效性。
Macrolide antibiotics penetrate cells, but the mechanism by which this occurs is unclear. The objective of this study was to characterize the mechanisms of clarithromycin uptake by gingival fibroblasts and oral epithelium. Cultured human gingival fibroblasts and SCC-25 cells were incubated with [H-3]-clarithromycin. We assayed clarithromycin transport by measuring cell-associated radioactivity over time. Fibroblasts and epithelial cells rapidly accumulated clarithro mycin, attaining steady-state intracellular concentrations within 15 minutes. Incubation in medium containing 2 mu g/mL clarithromycin yielded steady-state intracellular concentrations of 75.8 mu g/mL in fibroblasts and 6.6 mu g/mL in SCC-25 cells. Clarithromycin transport exhibited Michaelis-Menten kinetics and was inhibited below 37 degrees C. The Michaelis constants for fibro blasts and SCC-25 cells were 78.4 and 227 mu g/mL, respectively, while the maximum transport velocities were 264 and 381 ng/min/10(6) cells, respectively. Thus, both types of cells take up clarithromycin via a concentrative active transport system. By increasing intracellular clarithromycin levels, this system may enhance the effectiveness of clarithromycin against invasive periodontal pathogens.