Drug transporter expression in human macrophages
Drug transporter expression in human macrophages
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DOI：
10.1111/j.1472-8206.2010.00913.x
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发表时间：
2011-12-01
影响因子：
2.9
通讯作者：
Fardel, Olivier
中科院分区：
文献类型：
--
作者：
Moreau, Amelie;Le Vee, Marc;Fardel, Olivier
巨噬细胞是各种药物，特别是抗生素和抗病毒药物的主要细胞靶点。因此，可能决定这些细胞中药物细胞内蓄积的因素，特别是与药物转运蛋白活性相关的因素，可能很重要。因此，本研究旨在广泛表征从血液单核细胞产生的原代人巨噬细胞中溶质载体（SLC）和ATP结合盒（ABC）转运蛋白的表达。使用定量聚合酶链反应测定，发现这些细胞表现出非常高或高水平的浓度核苷转运蛋白（CNT）3、平衡核苷转运蛋白3、单羧酸转运蛋白（MCT）1、MCT 4、肽/组氨酸转运蛋白（PHT）1、PHT 2、有机阴离子转运多肽转运体2B 1和ABC泵多药耐药蛋白（MRP）1/ABCC 1和MRP 3/ABCC 3。相比之下，其他转运蛋白，包括外排泵ABCB 1/P-糖蛋白，被发现在较低的水平或不表达。同时，人巨噬细胞显示出对MCT底物乳酸盐和CNT底物尿苷的显著摄取，并且还显示出MRP底物羧基-2 '，7'-二氯荧光素的细胞外排。这些转运蛋白的功能性表达可能与靶向巨噬细胞的药物的细胞药代动力学有关。
Macrophages represent major cellular targets of various drugs, especially antibiotics and anti-viral drugs. Factors that may govern intracellular accumulation of drugs in these cells, especially those related to activity of drug transporters, are consequently likely important to consider. The present study was therefore designed to extensively characterize expression of solute carrier (SLC) and ATP-binding cassette (ABC) transporters in primary human macrophages generated from blood monocytes. Using quantitative polymerase chain reaction assays, these cells were found to exhibit very high or high levels of mRNA expression of concentrative nucleoside transporter (CNT) 3, equilibrative nucleoside transporter 3, monocarboxylate transporter (MCT) 1, MCT4, peptide/histidine transporter (PHT) 1, PHT2, organic anion transporting polypeptide transporter 2B1 and ABC pumps multidrug resistance protein (MRP) 1/ABCC1 and MRP3/ABCC3. By contrast, other transporters, including the efflux pump ABCB1/P-glycoprotein, were found at lower levels or were not expressed. Concomitantly, human macrophages displayed notable uptake of the MCT substrate lactate and of the CNT substrate uridine and also exhibited cellular efflux of the MRP substrate carboxy-2',7'-dichlorofluorescein. Such a functional expression of these transporters has likely to be considered with respect to cellular pharmacokinetics of drugs targeting macrophages.