Transient exposure of human eosinophils to the protein kinase C inhibitors CGP39-360, CGP41-251, and CGP44-800 leads to priming of the respiratory burst induced by opsonized particles.
We report that a transient incubation of human eosinophils with the protein kinase C (PKC) inhibitor CGP39-360 (staurosporine) or the more PKC-specific inhibitors CGP41-251 and CGP44-800 prior to activation of the respiratory burst with opsonized particles results in priming of this response. This priming effect was concentration dependent and occurred in the range in which the phorbol myristate acetate-induced respiratory burst was inhibited. CGP39-360 priming was minimally affected in Ca(2+)-depleted cells, indicating that an increase in [Ca2+]i is not important. Also, the binding of serum-treated zymosan (STZ) particles was strongly enhanced by the inhibitors. On the other hand, the release of platelet-activating factor (PAF) induced by opsonized particles was enhanced only by CGP39-360 and not by CGP41-251 and CGP44-800. Therefore, priming of the respiratory burst is not due to an aspecific enhancing effect of the inhibitors. These data indicate that different signal transduction routes are involved in priming of the STZ-induced respiratory burst and PAF release in human eosinophils.
van der Bruggen
T
T
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Kok
P T
PT
Blom
M
M
Verhoeven
A J
AJ
Raaijmakers
J A
JA
Lammers
J W
JW
Koenderman
L
L
D000470:Alkaloids / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects*; D006801:Humans; D009895:Opsonin Proteins / Q000378:metabolism; D009930:Organic Chemicals; D010972:Platelet Activating Factor / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D016897:Respiratory Burst / Q000187:drug effects*; D019311:Staurosporine / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism / Q000502:physiology
D000470:Alkaloids; C084561:CGP 44800; D004791:Enzyme Inhibitors; D009895:Opsonin Proteins; D009930:Organic Chemicals; D010972:Platelet Activating Factor; D015054:Zymosan; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium