Raghoebar M, van den Berg W B, van Ginneken C A
Int J Tissue React. 1987;9(3):255-61.
The present study concerns the established antirheumatic drug chloroquine (CQ) in relation to a possible target for drug therapy, the polymorphonuclear leucocyte (PMN). Its primary aim was to find out whether inflammatory conditions would influence the cell association of CQ. After a suitable ligand-binding assay was developed to measure the cellular association of CQ, the normal characteristics of the cellular transport of CQ were determined. The effect of the inflammatory conditions on CQ cell association was investigated with peripheral PMNs from rheumatoid arthritis (RA) patients, and with normal PMNs, in the absence and presence of the soluble cell-stimulators phorbol ester and chemotactic peptide. Under inflammatory conditions the intracellular concentration of CQ is reduced. This decrease is explained by three possibilities which are involved in cell activation: the leucocyte volume expansion, the cytoplasmic or lysosomal pH changes, and the exocytic release of the granules (degranulation). Our results suggest that this decrease will adversely affect the therapeutic effects, if the mode of anti-inflammatory action of CQ is related to the intracellular drug concentrations.
本研究关注已确定的抗风湿药物氯喹（CQ）与药物治疗的一个可能靶点——多形核白细胞（PMN）之间的关系。其主要目的是查明炎症状态是否会影响CQ与细胞的结合。在开发出一种合适的配体结合测定法以测量CQ的细胞结合后，确定了CQ细胞转运的正常特征。利用类风湿关节炎（RA）患者的外周PMN以及正常PMN，在不存在和存在可溶性细胞刺激剂佛波酯和趋化肽的情况下，研究了炎症状态对CQ细胞结合的影响。在炎症状态下，CQ的细胞内浓度会降低。这种降低可由涉及细胞活化的三种可能性来解释：白细胞体积膨胀、细胞质或溶酶体pH值变化以及颗粒的胞吐释放（脱颗粒）。我们的结果表明，如果CQ的抗炎作用方式与细胞内药物浓度相关，那么这种降低将对治疗效果产生不利影响。
