ROLE OF PROTEIN-KINASE-C ISOZYMES IN FC-GAMMA RECEPTOR-MEDIATED INTRACELLULAR KILLING OF STAPHYLOCOCCUS-AUREUS BY HUMAN MONOCYTES

Intracellular killing of Staphylococcus aureus by human monocytes afte r cross-linking Fc gamma R is known to be a phospholipase C (PLC)-depe ndent process. Activation of PLC leads to the formation of second mess engers that synergistically activate protein kinase C (PKC). The aim o f this study was to obtain more insight into the role of PKC in Fc gam ma R-mediated killing process. PKC inhibitors H-7 and staurosporine ma rkedly suppressed the killing of S. aureus by monocytes stimulated by cross-linking Fc gamma RI or -II. Cross-linking Fc gamma R caused a tr ansient increase in PKC activity in the membranes of monocytes, as mea sured by Ca2+/phospholipid-dependent phosphorylation of histone. Weste rn blot analysis revealed that cross-linking Fc gamma R stimulated a t ransient increase in PKC-beta in the membranes of monocytes with kinet ics that correlated closely with the translocation of PKC activity. Cr oss-linking Fc gamma R on monocytes also stimulated the translocation of PKC-epsilon but not PKC-alpha. PMA and 1-oleoyl-2-acetylglycerol (O AG), which caused translocation of PKC-alpha, -beta, and -epsilon, did not stimulate the killing process. Incubation with these PKC activato rs for 10 min rendered monocytes unresponsive to stimulation of killin g of S. aureus via Fc gamma R. It could be that activation of certain PKC isozymes, probably PKC-alpha and -epsilon, by these activators cau ses feedback inhibition of PLC and, consequently, the killing in monoc ytes, because PMA blocks the Fc gamma R-mediated intracellular inosito l(1,4,5)P-3 formation and PKC translocation. Together, our results ind icate that PKC isozymes play an important role in both stimulation and inhibition of the Fc gamma R-mediated intracellular killing of bacter ia by monocytes.