MODULATORY ROLE OF PROTEIN-KINASE-C ON THE SIGNAL-TRANSDUCTION PATHWAY UTILIZED BY PLATELET-ACTIVATING-FACTOR IN EOSINOPHIL ACTIVATION

To determine the role of protein kinase C (PKC) in the signal transduc tion in eosinophil pathways, we have assessed the effects of the phorb ol ester phorbol 12-acetate 13-myristate (PMA) on guinea pig peritonea l eosinophils challenged with platelet-activating factor (PAF). Pretre atment with PMA completely inhibited the PAF-induced release of eosino phil peroxidase (EPO) and superoxide anions and the rise in intracellu lar Ca2+ concentration ([Ca2+](i)), with IC(50)s of 2 to 10 nM. This i nhibition was reversed when the cells were preincubated with the PKC i nhibitor staurosporine for 5 min before the addition of PMA. Staurospo rine also inhibited PAF-induced EPO release but not the rise in [Ca2+] (i). The inactive ester 4 alpha-phorbol 12,13-didecanoate had no inhib itory effect on eosinophil activation. Finally, PMA inhibited the bind ing of the PAF antagonist [H-3]WEB 2086 to intact eosinophils. Taken t ogether, these data suggest that PKC may have a physiologic role in re gulating PAF-induced eosinophil responses through expression of PAF re ceptors on the cell surface.