PROTEIN-TYROSINE KINASE-ACTIVITY IS ESSENTIAL FOR FC-GAMMA RECEPTOR-MEDIATED INTRACELLULAR KILLING OF STAPHYLOCOCCUS-AUREUS BY HUMAN MONOCYTES

Our previous study revealed that the intracellular killing of Staphylo coccus aureus by human monocytes after cross-linking Fc gamma receptor I (Fc gamma RI) or Fc gamma RII is a phospholipase C (PLC)-dependent process. The aim of the present study was to investigate whether prote in tyrosine kinase (PTK) activity plays a role in the Fc gamma R-media ted intracellular killing of bacteria and activation of PLC in these c ells. The results showed that phagocytosis of bacteria by monocytes wa s not affected by the PTK inhibitors genistein and tyrphostin-47. The intracellular killing of S. aureus by monocytes after cross-linking Fc gamma RI or Fc gamma RII with anti-Fc gamma R monoclonal antibody and a bridging antibody or with human immunoglobulin G (IgG) was inhibite d by these compounds in a dose-dependent fashion. The production of O- 2(-) by monocytes after stimulation with IgG or IgG-opsonized S. aureu s was almost completely blocked by the PTK inhibitor. These results in dicate that inhibition of PTK impairs the oxygen-dependent bactericida l mechanisms of monocytes. Genistein and tyrphostin-47, which do not a ffect the enzymatic activity of purified PLC, prevented activation of PLC after cross-linking Fc gamma RI or Fc gamma RII, measured as an in crease in the intracellular inositol 1,4,5-trisphosphate concentration . Cross-linking Fc gamma RI or Fc gamma RII induced rapid tyrosine pho sphorylation of several proteins in monocytes, one of which was identi fied as PLC-gamma 1, and the phosphorylation could be completely block ed by PTK inhibitors, leading to the conclusion that activation of PLC after cross-linking Fc gamma R in monocytes is regulated by P?X activ ity. Together, these results demonstrate that PTK activity is essentia l for the activation of PLC which is involved in the Fc gamma R-mediat ed intracellular killing of S. aureus by human monocytes.