Stimulation of the intracellular killing of Staphylococcus aureus by human monocytes mediated by Fc gamma receptors I and II.

Abstract

Previous studies have shown that intracellular killing of bacteria by monocytes is stimulated by interaction between IgG and Fc gamma receptors (Fc gamma R) in the membrane of these cells. In the present study anti-Fc gamma R monoclonal antibodies (mAb) were used to investigate the 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 RII mAb, but not anti-Fc gamma RIII mAb, efficiently stimulated the intracellular 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 anti-mouse IgG enhanced this process. Since the NADPH oxidase inhibitor diphenyleneiodonium blocked the Fc gamma R-mediated intracellular killing of S. aureus, oxygen-dependent bactericidal mechanisms are most probably involved. Cross-linking Fc gamma RI or Fc gamma RII but not binding of the mAb to the Fc gamma R on monocytes activated phospholipase C, as demonstrated by the increase in the intracellular concentration of inositol-(1,4,5)-triphosphate. The enhanced intracellular killing stimulated by cross-linking Fc gamma R on monocytes was completely blocked 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 for the Fc gamma R-mediated intracellular killing of bacteria by monocytes. Together, these results demonstrate that cross-linking Fc gamma RI or Fc gamma RII is equally effective in stimulating the intracellular killing of bacteria by monocytes and that this stimulation is a phospholipase C-dependent process.