INTERFERON-GAMMA AFFECTS PROTEIN-KINASE-C ACTIVITY IN HUMAN NEUTROPHILS

Interferon-gamma (IFN-gamma) is a priming agent of polymorphonuclear n eutrophilic granulocyte (PMN) oxygen metabolism, and protein kinase C (PKC) is traditionally believed to play a central role in activation o f this oxygen metabolism, In the present study, we have shown that the PKC activity in PMN is affected by IFN-gamma. After only 2 minutes ex posure to IFN-gamma (100 U/ml), PKC activity was significantly increas ed in the noncytosolic fraction of the cells, This increase was transi ent, but toward the end of the priming period of 2 h, the membrane-ass ociated PKC activity increased again to about 152% of control, In the cytosolic fraction, a small and hardly detectable decrease in PKC acti vity was observed, Treatment of PMN with granulocyte-macrophage colony -stimulating factor (GM-CSF), another PMN priming agent, showed no sig nficant effects on the PKC activity, When the cells were stimulated wi th the bacterial peptide fMLP after a priming period with IFN-gamma or GM-CSF for 2 h, no significant difference between treated and control cells could be observed. PMN oxygen metabolism, measured by flow cyto metry as an accumulation of the fluorescent compound dichlorofluoresce in, was in these experiments significantly primed by IFN-gamma, both a t baseline and when stimulated with fMLP, The protein kinase C inhibit ors H7 and Ro31-8220 blocked the fMLP responses to some extent, but no t completely, However, no significant difference between fMLP response s in control and IFN-gamma-treated cells could be detected after admin istration of inhibitors. Our data therefore show that IFN-gamma affect s the PKC activity in human PMN and that PKC probably play some role i n the IFN-gamma priming of PMN oxygen metabolism,