ROLE OF PROTEIN-KINASE-C IN NEUTROPHIL SURVIVAL ENHANCED BY GRANULOCYTE-COLONY-STIMULATING FACTOR

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (10 ng/mL) prolonged human neutrophil survival in culture by at least 36 h ours. The addition of H-series compounds at concentrations that are co nsidered to inhibit both protein kinase C (PKC) and cyclic adenylate m onophosphate (cAMP)-dependent protein kinase (PKA) counteracted the ef fect of rhG-CSF. Concomitantly, the inhibition of nucleosomal DNA frag mentation by rhG-CSF was canceled. At lower concentrations, presumably capable of inhibiting only PKA, however, the compounds exhibited marg inal effects on rhG-CSF-mediated increase of cell survival. These PKC inhibitors did not influence the priming effect of rhG-CSF significant ly, as determined by O-2(-) production stimulated by N-formyl-L-methio nyl-L-leucyl phenylalanine (fMLP). Our results suggest that PKC plays an important role in the mechanism by which rhG-CSF promotes neutrophi l survival, in striking contrast with the priming effect elicited by r hG-CSF.