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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. |
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