Elferink J G, de Koster B M
Department of Medical Biochemistry, Leiden University, The Netherlands.
Biochem Pharmacol. 1998 Feb 1;55(3):305-12. doi: 10.1016/s0006-2952(97)00468-1.
The sulfhydryl-reactive compound thimerosal caused a chemotactic stimulation of neutrophil migration at low concentrations and inhibition of chemoattractant-stimulated chemotaxis at high concentrations. Thiosalicylic acid, an analog of thimerosal devoid of mercury, also stimulated migration at low concentrations and caused inhibition at higher concentrations, though the inhibitory effect was less pronounced than that of thimerosal. These results indicate that the stimulatory effect of thimerosal on migration is due to the thiosalicylic acid moiety of the molecule. In contrast with thimerosal which, especially at higher concentrations than required for optimal stimulation of migration, caused an increase in cytosolic free calcium ([Ca2+]i), thiosalicylic acid had no effect on [Ca2+]i of the neutrophil. This suggests that the presence of mercury is decisive for the calcium-mobilizing effect, but not for stimulation of migration, and that mobilization of calcium and activation of migration are not related. Thimerosal caused a strong increase of CD11b expression in neutrophils in suspension, especially at inhibitory concentrations, while thiosalicylic acid had no effect on CD11b expression. This could mean (but does not prove) that CD11b expression is more related to the calcium-mobilizing effect of thimerosal than to its stimulation of migration.
巯基反应性化合物硫柳汞在低浓度时可引起中性粒细胞迁移的趋化性刺激,而在高浓度时则抑制趋化因子刺激的趋化作用。硫柳汞的类似物硫代水杨酸不含汞,在低浓度时也能刺激迁移,在较高浓度时则产生抑制作用,不过其抑制作用不如硫柳汞明显。这些结果表明,硫柳汞对迁移的刺激作用归因于该分子的硫代水杨酸部分。与硫柳汞相反,尤其是在高于最佳迁移刺激所需浓度时,硫柳汞会导致细胞内游离钙([Ca2+]i)增加,而硫代水杨酸对中性粒细胞的[Ca2+]i没有影响。这表明汞的存在对钙动员效应起决定性作用,但对迁移刺激不起作用,且钙的动员与迁移的激活无关。硫柳汞可使悬浮的中性粒细胞中CD11b表达显著增加,尤其是在抑制浓度时,而硫代水杨酸对CD11b表达没有影响。这可能意味着(但未得到证实)CD11b表达与硫柳汞的钙动员效应比与它对迁移的刺激作用更相关。