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 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 IO4 augmented their cytotoxicity against K562 myelogenous leukemia cells. IO4 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 IO4. Moreover, IO4 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 microM and significantly reduced the enhanced cytotoxicity of PBL at the same concentration. These results indicated 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.
Noda
I
I
Department of Otolaryngology, Fukui Medical University, Japan. ichiron@fmsrsa.fukui-med.ac.jp
Fujieda
S
S
Saito
H
H
Saito
T
T
Otsubo
T
T
Yagita
M
M
D000255:Adenosine Triphosphate / Q000097:blood; D001880:Boranes / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*
D001880:Boranes; D004791:Enzyme Inhibitors; D008934:Mitogens; D010504:Periodic Acid; D000255:Adenosine Triphosphate; C009288:metaperiodate; D011493:Protein Kinase C