Climax J, Lenehan T J, Lambe R, Kenny M, Caffrey E, Darragh A
J Antimicrob Chemother. 1986 Apr;17(4):489-98. doi: 10.1093/jac/17.4.489.
The uptake of sulphamethoxazole, sulphadiazine, sulphamerazine, sulphanilamide, trimethoprim and brodimoprim by human peripheral blood leucocytes, has been investigated. High performance liquid chromatography (HPLC) was used to assay drug concentrations before and after incubation with leucocyte suspensions. Using radiolabelled material the intracellular localization of two of these compounds was also determined. The results indicated that all the investigated drugs were taken up by leucocytes. Differential studies demonstrated that mononuclear cells accumulated higher drug concentrations (0.13-0.55 microgram/10(7) cells), than resting neutrophils (0.02-0.26 microgram/10(7) cells) with the exception of sulphanilamide, which was taken up to a greater extent by neutrophils (0.75 microgram/10(7) cells). During neutrophil phagocytosis intracellular levels of all the drugs except brodimoprim increased from 3 to 130-fold as compared to resting neutrophils. The uptake of 14C-sulphanilamide and 14C-trimethoprim, in neutrophils and mononuclear blood cells, as assessed by measurement of the cell-associated radioactivity, correlated well with that determined by the HPLC procedure. In the intracellular localization studies 14C-sulphanilamide and 14C-trimethoprim exhibited similar distribution profiles. In neutrophils, 35-40% of radiolabelled drug was located in both the microsome and cytosol fractions whereas in peripheral blood mononuclear cells 40-60% was found in the cytosol and 10-20% in the microsome fraction. The results of this study suggest that, following activation, leucocytes may actively transport these drugs and release them locally at sites of infection. The ability of neutrophils to further concentrate the drugs during phagocytosis may result in reduced survival time of some ingested bacteria. These concepts may be important in designing treatment stratagems for intracellular pathogens.
已对人外周血白细胞对磺胺甲恶唑、磺胺嘧啶、磺胺甲基嘧啶、磺胺、甲氧苄啶和溴莫普明的摄取情况进行了研究。采用高效液相色谱法（HPLC）测定白细胞悬液孵育前后的药物浓度。还使用放射性标记物质确定了其中两种化合物的细胞内定位。结果表明，所有研究的药物均被白细胞摄取。差异研究表明，除磺胺外，单核细胞积累的药物浓度（0.13 - 0.55微克/10⁷细胞）高于静息中性粒细胞（0.02 - 0.26微克/10⁷细胞），磺胺被中性粒细胞摄取的程度更高（0.75微克/10⁷细胞）。在中性粒细胞吞噬过程中，除溴莫普明外，所有药物的细胞内水平与静息中性粒细胞相比增加了3至130倍。通过测量细胞相关放射性评估，中性粒细胞和单核血细胞中¹⁴C - 磺胺和¹⁴C - 甲氧苄啶的摄取与HPLC法测定的结果相关性良好。在细胞内定位研究中，¹⁴C - 磺胺和¹⁴C - 甲氧苄啶表现出相似的分布模式。在中性粒细胞中，35 - 40%的放射性标记药物位于微粒体和胞质溶胶部分，而在外周血单核细胞中，40 - 60%位于胞质溶胶中，10 - 20%位于微粒体部分。本研究结果表明，激活后白细胞可能会主动转运这些药物并在感染部位局部释放。中性粒细胞在吞噬过程中进一步浓缩药物的能力可能导致一些被吞噬细菌的存活时间缩短。这些概念在设计细胞内病原体治疗策略时可能很重要。
