Gabler W L, Smith J, Tsukuda N
Department of Oral Molecular Biology, School of Dentistry, Oregon Health Sciences University, Portland.
Res Commun Chem Pathol Pharmacol. 1992 Nov;78(2):151-60.
Tetracyclines (Tc's) have the ability to inhibit neutrophil (PMN) functions which may be of value in the treatment of neutrophil-driven pathologic processes. However, long term use of Tc's frequently lead to emergence of antibiotic resistant strains of bacteria. A chemically modified analogue of Tc, 4DTc, having minimal antibiotic activity was compared to Dc, a member of the Tc family, for its ability to inhibit neutrophil functions. 4DTc was significantly less effective at inhibiting PMN superoxide synthesis, PMA-induced degranulation and PMN-mediated RBC lysis than was Dc. 4DTc and Dc were equally as effective inhibiting monocyte, but not PMN, adherence to gelatin-coated surfaces. When incubated in media containing varying 4DTc or Dc concentrations, Dc accumulated in RBC's and PMN's at levels 3 times greater than that found for similar media levels of 4DTc. The data suggest that the lesser ability of 4DTc to inhibit several PMN functions as compared to Dc may be related to its reduced intracellular accumulation. It also suggest that Tc inhibition of monocyte adherence may be more influenced by extracellular than intracellular processes.
四环素（Tc）具有抑制中性粒细胞（PMN）功能的能力，这在治疗由中性粒细胞驱动的病理过程中可能具有重要价值。然而，长期使用四环素常常会导致抗生素耐药菌株的出现。将一种化学修饰的四环素类似物4DTc（其抗生素活性极小）与四环素家族成员强力霉素（Dc）进行比较，以研究它们抑制中性粒细胞功能的能力。在抑制PMN超氧化物合成、佛波酯（PMA）诱导的脱颗粒以及PMN介导的红细胞溶解方面，4DTc的效果明显不如强力霉素。在抑制单核细胞（而非PMN）黏附于明胶包被表面方面，4DTc和强力霉素的效果相当。当在含有不同浓度4DTc或强力霉素的培养基中孵育时，强力霉素在红细胞和PMN中的积累水平比在含有相似培养基水平4DTc的情况下高3倍。数据表明，与强力霉素相比，4DTc抑制多种PMN功能的能力较弱可能与其细胞内积累减少有关。这也表明，四环素对单核细胞黏附的抑制作用可能更多地受细胞外而非细胞内过程的影响。
