EFFECTS OF PROTEIN-KINASE-C ACTIVATORS ON HUMAN BASOPHILS

In the present study the effects of different activators of protein kinase C (PKC) on histamine release from human basophils were studied. The phorbol esters 12-O-tetradecanoyl-phorbol-13-acetate (TPA), phorbol-12,13-dibutyrate (PDBu), phorbol-12,13-didecanoate, and the non-phorbol mezerein induced a dose-dependent mediator release, whereas 4alpha-phorbol-12,13-didecanoate and 4alpha-phorbol, which both do not activate isolated PKC in vitro, were inactive. However, PDBu and mezerein were significantly more active than TPA, indicating that histamine releasing capacity was independent of their activity on PKC. We suggest, therefore, that different PKC isotypes with distinct biochemical characteristics are activated by these compounds. Alternatively, additional PKC-independent mechanisms might explain our findings. Moreover, a direct comparison of TPA-induced and IgE-mediated histamine release, using basophils from the same subjects, revealed a poor correlation. This may confirm previous observations on their differing effects on PKC levels.