Graevskaya Elizabeth E, Yasutake Akira, Aramaki Ryoji, Rubin Andrew B
Moscow State University, Biological Faculty, Department of Biophysics, 119899, Vorobjovy Gory, Moscow, Russia.
Arch Toxicol. 2003 Jan;77(1):17-21. doi: 10.1007/s00204-002-0408-9. Epub 2002 Oct 23.
Methylmercury chloride (MeHgCl) is well known as a significant environmental hazard, particularly as a modulator of the immune system. As it is acknowledged that the critical effector cells in the host response participating in various biological responses are mast cells, we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. We investigated the effects of methylmercury on the rat mast cell degranulation induced by non-immunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. Using the cells prepared from methylmercury-intoxicated rats through a 5-day treatment of MeHgCl (10 mg/kg/day), we observed the suppression of calcium ionophore A23187- and 48/80-induced histamine release, which was enhanced with time after treatment. Similar suppression was observed in the ionophore-stimulated release, when cells were prepared from rat with a single treatment of MeHgCl (20 mg/kg). It should be noted that when cells from the control rat were pre-incubated with methylmercury in vitro at a 10(-8) M concentration for 10 min, A23187 and compound 48/80-stimulated histamine release was significantly enhanced. However, when the pre-incubation period was prolonged to 30 min, the release was suppressed. An increase in the methylmercury concentration to 10(-6) M also suppressed the histamine release. These results show that methylmercury treatment can modify mast cell function depending on concentration and time, and might provide an insight into the role of mast cells in the development of methylmercury-stimulated effects.
甲基氯化汞(MeHgCl)是一种广为人知的重大环境危害物,尤其是作为免疫系统的调节剂。由于人们认识到参与各种生物反应的宿主反应中的关键效应细胞是肥大细胞,我们试图确定肥大细胞在甲基汞诱发效应发展过程中可能发挥的作用。我们在体内和体外研究了甲基汞对非免疫刺激(组胺选择性释放剂、化合物48/80和钙离子载体A23187)诱导的大鼠肥大细胞脱颗粒的影响。通过用MeHgCl(10毫克/千克/天)进行为期5天的处理,使用从甲基汞中毒大鼠制备的细胞,我们观察到钙离子载体A23187和48/80诱导的组胺释放受到抑制,且这种抑制作用在处理后随时间增强。当用单次剂量的MeHgCl(20毫克/千克)处理大鼠并制备细胞时,在离子载体刺激的释放中也观察到了类似的抑制作用。应当指出的是,当将对照大鼠的细胞在体外以10^(-8) M的浓度与甲基汞预孵育10分钟时,A23187和化合物48/80刺激的组胺释放显著增强。然而,当预孵育时间延长至30分钟时,释放受到抑制。将甲基汞浓度增加到10^(-6) M也抑制了组胺释放。这些结果表明,甲基汞处理可根据浓度和时间改变肥大细胞功能,并可能为肥大细胞在甲基汞刺激效应发展中的作用提供见解。