STIMULATION OF THE INTRACELLULAR KILLING OF STAPHYLOCOCCUS-AUREUS BY HUMAN MONOCYTES MEDIATED BY FC-GAMMA RECEPTOR-I AND RECEPTOR-II

Previous studies have shown that intracellular killing of bacteria by monocytes is stimulated by interaction between IgG and Fc gamma recept ors (Fc gamma R) in the membrane of these cells. In the present study anti-Fc gamma R monoclonal antibodies (mAb) were used to investigate t he relative contributions of the various classes of Fc gamma R to the intracellular killing of Staphylococcus aureus by human monocytes and the biochemical pathways involved. Anti-Fc gamma RI or anti-Fc gamma R II mAb, but not anti-Fc gamma RIII mAb, efficiently stimulated the int racellular killing of bacteria by monocytes. Cross-linking Fc gamma RI or Fc gamma RII, but not Fc gamma RIII, on monocytes with mouse anti- Fc gamma R mAb followed by bridging with F(ab')(2) fragments of goat a nti-mouse IgG enhanced this process. Since the NADPH oxidase inhibitor diphenyleneiodonium blocked the Fc gamma R-mediated intracellular kil ling of S. aureus, oxygen-dependent bactericidal mechanisms are most p robably involved. Cross-linking Fc gamma RI or Fc gamma RII but not bi nding of the mAb to the Fc gamma R on monocytes activated phospholipas e C, as demonstrated by the increase in the intracellular concentratio n of inositol-(1,4,5)-triphosphate. The enhanced intracellular killing stimulated by cross-linking Fc gamma R on monocytes was completely bl ocked by U-73122, an inhibitor of phospholipase C-dependent processes. Protein kinase C activity but not the rise in the cytosolic free Ca+ concentration or pertussis toxin-sensitive G proteins, is essential f or the Fc gamma R-mediated intracellular killing of bacteria by monocy tes. Together, these results demonstrate that cross-linking Fc gamma R I or Fc gamma RII is equally effective in stimulating the intracellula r killing of bacteria by monocytes and that this stimulation is a phos pholipase C-dependent process.