Protein kinase C mediates human neutrophil cytotoxicity.
Human neutrophils stimulated with phorbol myristate acetate were able to damage human erythroleukemic K562 cells, in the absence of specific antibody, as assessed by a two hour 51Cr release assay. Neutrophils treated with formyl-peptide fMet-Leu-Phe did not display tumoricidal response, but the addition of diacylglycerol kinase inhibitor R59022 together with formyl-peptide induced the cytotoxic capacity against tumor target cells. Phorbol ester is a potent activator of certain functions of neutrophils because of its ability to directly and irreversibly stimulate protein kinase C; formyl-peptide, on the contrary, activates protein kinase C by inducing a rapid and transient production of diacylglycerol, that is quickly metabolized. The addition of an inhibitor of diacylglycerol kinase, R59022, however potentiated the action of formyl-peptide. These results indicate that protein kinase C is involved in the tumoricidal activity of neutrophils against K562 cells, and that maximal activation of the enzyme is required to achieve the cytotoxic response.
Gavioli
R
R
Istituto di Chimica Biologica, Università di Ferrara, Italy.
Spisani
S
S
Giuliani
A
A
Traniello
S
S
D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019852:Diacylglycerol Kinase; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000502:physiology*; D011744:Pyrimidinones / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D011744:Pyrimidinones; D013844:Thiazoles; D009240:N-Formylmethionine Leucyl-Phenylalanine; C047505:R 59022; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate