DIFFERENTIAL REGULATION OF PHOSPHOLIPASE-D AND PHOSPHOLIPASE-C BY PROTEIN-KINASE-C-BETA AND PROTEIN-KINASE-C-DELTA IN LIVER MACROPHAGES

We have studied activation of phospholipase (PL) C and PLD in liver ma crophages labelled with [H-3]arachidonic acid. Zymosan, phorbol 12-myr istate 13-acetate (PMA), A23187 and fluoride but not arachidonic acid or lipopolysaccharide (LPS) induce an activation of PLD ([H-3]phosphat idylethanol (PEt) accumulation). An activation of PLC ([3H]diacylglyce rol (DAG) accumulation) is measured with zymosan, PMA and fluoride but not with A23187, LPS or arachidonic acid whereas inositol phosphates are formed with zymosan, only. Removal of extracellular calcium reduce s the formation of [H-3]PEt and [H-3]DAG while pretreatment of the cel ls with dexamethasone reduces [H-3]PEt formation, only. PMA- and zymos an-induced activation of PLD and PMA-induced activation of PLC both se em to be mediated by protein kinase (PK) C-beta whereas zymosan-induce d activation of PLC is negatively controlled by PKC-delta. We could fu rthermore present evidence that the release of [H-3]arachidonic acid i n these cells occurs independent of an activation of PLD.