ENHANCEMENT OF CYTOLYTIC ACTIVITY OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES BY SODIUM PERIODATE (IO4) POSSIBLE INVOLVEMENT OF PROTEIN-KINASE-C

Sodium periodate (IO4) exerts a number of biological effects including the enhancement of lymphocyte activation. In this study, we investiga ted 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 IO4 augmented their cytotoxicity aga inst K562 myelogenous leukemia cells. IO4 oxidative treatment increase d the frequency of effector-to-target cell binding. It also increased cellular ATP levels in effector cells, suggesting that the post-bindin g cytolytic functions of these cells were also enhanced after treatmen t with IO4. Moreover, IO4 treatment significantly increased the protei n kinase C (PKC) activity of effector cells and induced the translocat ion of activity in the membrane fraction from the cytosol. H-7, a pote nt PKC inhibitor, significantly reduced this enhancement of membrane-a ssociated PKC activity at 10 mu M and significantly reduced the enhanc ed cytotoxicity of PBL at the same concentration. These results indica ted that IO4 enhanced the binding capacity and post-binding cytolytic functions of PBL and that PKC activation was one mechanism to explain the IO4-induced cellular activation. (C) 1998 International Society fo r Immunopharmacology. Published by Elsevier Science Ltd. All rights re served.