4-Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro.
4-Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro.
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4-喹诺酮类药物影响体外人淋巴细胞的细胞周期进程和功能。
DOI：
10.1128/aac.31.5.768
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发表时间：
1987
影响因子：
4.9
通讯作者：
Tedder,TF
中科院分区：
文献类型：
--
作者：
Forsgren,A;Schlossman,SF;Tedder,TF
大多数抗菌药物不影响人淋巴细胞功能，但少数具有抑制作用。相反，在这些研究中观察到在4-喹诺酮类药物存在下[3 H]胸苷掺入显著增加。当8种新的4-喹诺酮衍生物，环丙沙星，诺氟沙星，氧氟沙星，A-56619，A-56620，阿米福隆，依诺沙星和培氟沙星，在1.6至6.25微克/毫升的浓度下暴露5天时，植物血凝素刺激的人淋巴细胞对DNA（三氯乙酸可沉淀）的[3 H]胸苷摄取显著增加。四个抗菌活性较低的4-喹诺酮类（萘啶酸，西诺沙星，氟甲喹，哌哌甲酯酸）刺激[3 H]胸苷掺入仅在较高浓度或根本没有。动力学研究表明，掺入[3 H]胸苷不受影响或略有抑制环丙沙星2天后，植物血凝素刺激，但增加了第3至6天。在5 ~ 20 μ g/ml的环丙沙星浓度下，植物血凝素刺激后第1 ~ 6天的[3 H]胸苷总掺入量增加了42%~ 45%。增加[3 H]胸苷掺入时，也看到人淋巴细胞刺激有丝分裂原以外的植物血凝素。在培养开始时加入环丙沙星对[3 H]胸苷掺入的影响比后来加入时更明显。尽管DNA合成明显增加，淋巴细胞的生长被20微克/毫升的环丙沙星抑制，细胞周期分析表明，环丙沙星抑制通过细胞周期的进展。此外，在5微克环丙沙星/ml时，由美洲商陆有丝分裂原刺激的EB病毒的人淋巴细胞的免疫球蛋白分泌被抑制约50%。这些结果表明，4-喹诺酮类药物也可能影响真核细胞的功能在体外，但需要额外的研究，以建立在体内的相关性。
Most antibacterial agents do not affect human lymphocyte function, but a few are inhibitory. In contrast, a pronounced increase in the incorporation of [3H]thymidine in the presence of 4-quinolones was observed in these studies. The uptake of [3H]thymidine into DNA (trichloroacetic acid precipitable) was significantly increased in phytohemagglutinin-stimulated human lymphocytes when they were exposed to eight new 4-quinolone derivatives, ciprofloxacin, norfloxacin, ofloxacin, A-56619, A-56620, amifloxacin, enoxacin, and pefloxacin, at 1.6 to 6.25 micrograms/ml for 5 days. Four less antibacterially active 4-quinolones (nalidixic acid, cinoxacin, flumequine, and pipemidic acid) stimulated [3H]thymidine incorporation only at higher concentrations or not at all. Kinetic studies showed that incorporation of [3H]thymidine was not affected or slightly inhibited by ciprofloxacin 2 days after phytohemagglutinin stimulation but was increased on days 3 to 6. The total incorporation of [3H]thymidine from day 1 to day 6 after phytohemagglutinin stimulation was increased by 42 to 45% at 5 to 20 micrograms of ciprofloxacin per ml. Increased [3H]thymidine incorporation was also seen when human lymphocytes were stimulated with mitogens other than phytohemagglutinin. Ciprofloxacin added at the start of the culture had a more pronounced effect on [3H]thymidine incorporation than when added later. In spite of the apparent increase in DNA synthesis, lymphocyte growth was inhibited by 20 micrograms of ciprofloxacin per ml, and cell cycle analysis showed that ciprofloxacin inhibited progression through the cell cycle. In addition, immunoglobulin secretion by human lymphocytes stimulated by pokeweed mitogen for Epstein-Barr virus was inhibited by approximately 50% at 5 micrograms of ciprofloxacin per ml. These results suggest that the 4-quinolone drugs may also affect eucaryotic cell function in vitro, but additional studies are needed to establish an in vivo relevance.