Protein kinase C mediates human neutrophil cytotoxicity.

Abstract

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.

• Authors: R Gavioli, S Spisani, A Giuliani, S Traniello
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 148 Issue 3 Pg. 1290-4 (Nov 13 1987) ISSN: 0006-291X [Print] United States
• PMID: 2825682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pyrimidinones
• Thiazoles
• N-Formylmethionine Leucyl-Phenylalanine
• R 59022
• Phosphotransferases
• Diacylglycerol Kinase
• Protein Kinase C
• Tetradecanoylphorbol Acetate

Topics

• Cytotoxicity, Immunologic (drug effects)
• Diacylglycerol Kinase
• Humans
• N-Formylmethionine Leucyl-Phenylalanine (pharmacology)
• Neutrophils (physiology)
• Phosphotransferases (antagonists & inhibitors)
• Protein Kinase C (physiology)
• Pyrimidinones (pharmacology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Thiazoles (pharmacology)