SIGNAL-TRANSDUCTION PATHWAYS LEADING TO ARACHIDONIC-ACID RELEASE FROMNEUTROPHILIC HL-60 CELLS - THE INVOLVEMENT OF G-PROTEIN, PROTEIN-KINASE-C AND PHOSPHOLIPASE A(2)

Arachidonic acid release from undifferentiated and neutrophilic HL-60 cells was studied. In neutrophilic cells it was stimulated by N-formyl -Met-Leu-Phe and mastoparan by a mechanism involving G(i) protein and phospholipase C and was largely dependent on diacyglycerol lipase. Max imum release from both cell types was achieved with fluoride and requi red cellular energy. Inhibitor studies suggest that arachidonic acid r elease by fluoride stimulation leads to phospholipase A2 activation wi th signal transduction involving phospholipase C and protein kinase C. Only neutrophilic cells responded to phorbol ester if Ca2+-ionophore was simultaneously present but this effect was abolished by extended t reatment with phorbol ester. Thus, protein kinase C plays a major role in highly stimulated neutrophilic cells. These cells are differently equipped with protein kinase C isoenzymes compared with undifferentia- ted cells. In contrast, both cell types contain similar levels of typ e II and cytosolic phospholipases A(2), the former being by far the mo re prevalent.