Morita M, Tsuruta S, Mori K J, Mayumi M, Mikawa H
Dept of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Eur Respir J. 1990 Nov;3(10):1173-8.
The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.
利用针对丝状肌动蛋白（F-肌动蛋白）的特异性试剂，通过流式细胞术检测了酮替芬对人嗜酸性粒细胞白血病细胞系EoL-1中血小板活化因子（PAF）诱导的肌动蛋白聚合的抑制作用。肌动蛋白聚合被认为对细胞运动、趋化性和化学增活作用至关重要，因此它反映了PAF刺激的EoL-1细胞的趋化反应。未受刺激的EoL-1细胞几乎没有PAF诱导的肌动蛋白聚合，而用人ATL细胞系HIL-3的上清液（HIL-3 sup）培养9天的EoL-1细胞在用PAF刺激时则表现出明显的肌动蛋白聚合。在PAF浓度为10^(-10) M至10^(-6) M时，PAF诱导的EoL-1细胞中的肌动蛋白聚合呈剂量依赖性，在PAF浓度为10^(-7) M时观察到最大效应。PAF的特异性拮抗剂CV-3988在浓度为10^(-5) M时可抑制PAF诱导的EoL-1细胞中80%的肌动蛋白聚合。酮替芬在浓度为10^(-9) M至10^(-5) M时以剂量依赖性方式抑制PAF诱导的EoL-1细胞的肌动蛋白聚合高达40%。这些结果表明，酮替芬可能通过抑制PAF诱导的嗜酸性粒细胞趋化作用在预防过敏性疾病中嗜酸性粒细胞诱导的炎症中发挥重要作用。
