Enhancement of Zymosan-Induced Respiratory Burst of Rat Neutrophils by Lead in Vitro

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The effect of Pb^<2+> on serum-treated zymosan (STZ)-induced O_2 consumption of rat peritoneal neutrophils was studied. Pb^<2+> was found to mimic effectively the enhancing action of Ca^<2+> on the O_2 consumption depending on the concentration up to about 80 μM. However, at concentrations over 80 μM, Pb^<2+> inhibited the O_2 consumption. The enhancing effect of Pb^<2+> on the O_2 consumption was further examined using the intracellularly Ca^<2+> -depleted neutrophils. Pb^<2+> also enhanced the O_2 consumption of the Ca^<2+>-depleted cells as effectively as Ca^<2+>. The Pb^<2+>-enhanced O_2 consumption of the Ca^<2+>-depleted cells was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) based on its calmodulin antagonistic action. The effect of Pb^<2+> on the activity of activator-deficient 3', 5'-cyclic nucleotide phosphodiesterase (PDE), a calmodulin-dependent enzyme, was examined. Pb^<2+> activated PDE as effectively as Ca^<2+> only in the presence of calmodulin. The Pb^<2+>-activated PDE activity was also inhibited by W-7 only in the presence of calmodulin. These results indicated that Pb^<2+> could replace Ca^<2+> in the activation process(es) of the respiratory burst, suggesting a possible involvement of calmodulin in the enhancing mechanism of the O_2 consumption by Pb^<2+>.
社団法人日本薬学会の論文
1989-05-25