Phorbol ester-induced suppression of leukotriene C4 synthase activity in human granulocytes

The effect of the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), on the metabolism of exogenous leukotriene (LT)A4 in human granulocytes was investigated. After incubation with LTA4 decreased levels of LTC4 but not LTB4 were observed in granulocyte suspensions pretreated with PMA. This finding could in part be ascribed to oxidative metabolism of LTC4, since PMA induced a rapid degradation of exogenously added LTC4. After blocking of LTC4 metabolism with the H2O2 scavenger catalase, a PMA-provoked suppression of the conversion of LTA4 to LTC4 was observed, indicating PKC-dependent regulation of LTC4 synthase activity. This effect, as well as PMA-induced degradation of LTC4 was prevented by specific protein kinase C inhibitors.