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.
AuthorsR Gavioli, S Spisani, A Giuliani, S Traniello
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 148 Issue 3 Pg. 1290-4 (Nov 13 1987) ISSN: 0006-291X [Print] UNITED STATES
PMID2825682 (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
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: