Enhancement of cytolytic activity of human peripheral blood lymphocytes by sodium periodate (IO4) possible involvement of protein kinase C

Abstract

Sodium periodate (IO 4) exerts a number of biological effects including the enhancement of lymphocyte activation. In this study, we investigated its effects on cytotoxicity of human peripheral blood lymphocytes (PBL) and explored the mechanism whereby it exerted these effects. In vitro treatment of human PBL with IO 4 augmented their cytotoxicity against K562 myelogenous leukemia cells. IO 4 oxidative treatment increased the frequency of effector-to-target cell binding. It also increased cellular ATP levels in effector cells, suggesting that the post-binding cytolytic functions of these cells were also enhanced after treatment with IO 4. Moreover, IO 4 treatment significantly increased the protein kinase C (PKC) activity of effector cells and induced the translocation of activity in the membrane fraction from the cytosol. H-7, a potent PKC inhibitor, significantly reduced this enhancement of membrane-associated PKC activity at 10 μM and significantly reduced the enhanced cytotoxicity of PBL at the same concentration. These results indicated that IO 4 enhanced the binding capacity and post-binding cytolytic functions of PBL and that PKC activation was one mechanism to explain the IO 4-induced cellular activation.