Am. J. Respir. Cell Mol. Biol., Vol 11, No. 5, Nov 1994, 593-599.
Modulatory role of protein kinase C on the signal transduction pathway utilized by platelet-activating factor in eosinophil activation
C Kroegel, MA Giembycz, H Matthys, J Westwick and PJ Barnes
Department of Thoracic Medicine, National Heart and Lung Institute, Brompton Hospital, London, United Kingdom.
To determine the role of protein kinase C (PKC) in the signal transduction
in eosinophil pathways, we have assessed the effects of the phorbol ester
phorbol 12-acetate 13-myristate (PMA) on guinea pig peritoneal eosinophils
challenged with platelet-activating factor (PAF). Pretreatment with PMA
completely inhibited the PAF-induced release of eosinophil peroxidase (EPO)
and superoxide anions and the rise in intracellular Ca2+ concentration
([Ca2+]i), with IC50s of 2 to 10 nM. This inhibition was reversed when the
cells were preincubated with the PKC inhibitor staurosporine for 5 min
before the addition of PMA. Staurosporine also inhibited PAF-induced EPO
release but not the rise in [Ca2+]i. The inactive ester 4 alpha-phorbol
12,13-didecanoate had no inhibitory effect on eosinophil activation.
Finally, PMA inhibited the binding of the PAF antagonist [3H]WEB 2086 to
intact eosinophils. Taken together, these data suggest that PKC may have a
physiologic role in regulating PAF-induced eosinophil responses through
expression of PAF receptors on the cell surface.
