Gabler W L
Department of Biochemistry, School of Dentistry, Oregon Health Sciences University, Portland.
Res Commun Chem Pathol Pharmacol. 1991 Apr;72(1):39-51.
Tetracyclines (Tc's) have anti-inflammatory properties unrelated to their antibiotic activities. Their anti-inflammatory property, in part, results from the ability of members of this family of antibiotic to inhibit neutrophil functions. There are marked differences in the ability of different Tc's to suppress neutrophils which may relate to their ability to cross the plasma membrane. To gain insight into the mechanism of Tc inhibition of neutrophils and the reason for the differences in antineutrophil effect of Tc's, we studied the flux and sequestration of Tc's in blood cells. Using centrifugation and a dibutylphthalate scrubber system we found that doxycycline (Dc) was rapidly taken up by blood cells reaching intracellular concentrations several times that found in the medium. Dc also rapidly effluxed when antibiotic loaded cells were placed in drug free medium. While Ca2+, Mg2+ nor protein separately were effective inhibitors of Dc influx, when divalent cations and proteins were combined Dc uptake was markedly suppressed. Tc uptake by blood cells ranked Dc greater than chlortetracycline = tetracycline greater than oxytetracycline, a ranking similar to that reported for neutrophil inhibition by members of the Tc family, suggesting that intracellular accumulation of drug is an important facet of Tc suppression of neutrophil function.
四环素（Tc's）具有与其抗生素活性无关的抗炎特性。它们的抗炎特性部分源于该抗生素家族成员抑制中性粒细胞功能的能力。不同的Tc's抑制中性粒细胞的能力存在显著差异，这可能与其穿越质膜的能力有关。为了深入了解Tc抑制中性粒细胞的机制以及Tc's抗中性粒细胞作用差异的原因，我们研究了Tc's在血细胞中的通量和滞留情况。通过离心和邻苯二甲酸二丁酯洗涤系统，我们发现强力霉素（Dc）被血细胞迅速摄取，细胞内浓度达到培养基中浓度的数倍。当将加载抗生素的细胞置于无药物培养基中时，Dc也会迅速流出。虽然单独的Ca2+、Mg2+或蛋白质都不是Dc流入的有效抑制剂，但当二价阳离子和蛋白质结合时，Dc的摄取会明显受到抑制。血细胞对Tc的摄取情况为Dc大于金霉素=四环素大于土霉素，这一排序与Tc家族成员对中性粒细胞抑制作用的报道排序相似，表明药物在细胞内的积累是Tc抑制中性粒细胞功能的一个重要方面。
