Arachidonic acid, but not its metabolites, is essential for Fc gamma R-stimulated intracellular killing of Staphylococcus aureus by human monocytes

Since arachidonic acid (AA) production by phospholipase A(2) (PLA(2)) is es sential for the Fc gamma receptor (Fc gamma R)-mediated respiratory burst a nd phagocytosis of opsonized erythrocytes by monocytes and macrophages, we focused in this study on the role of AA and its metabolites in the Fc gamma R-stimulated intracellular killing of Staphylococcus aureus by human monoc ytes. The results revealed that the PLA(2) inhibitors, but not inhibitors o f cyclo-oxygenase and lipoxygenase, markedly suppressed the Fc gamma R-medi ated killing process. The production of O-2(-) by monocytes upon Fc gamma R cross-linking was inhibited by 4-bromophenacyl bromide in a dose-dependent fashion, indicating that inhibition of PLA(2) activity impairs the oxygen- dependent bactericidal mechanisms of monocytes, which could be partially re stored by addition of exogenous AA and docosahexaenoic acid, but not myrist ic acid. These polyunsaturated fatty acids, but not myristic acid, stimulat ed the intracellular killing of S. aureus by monocytes, although not as eff ectively as Fc gamma R cross linking. Furthermore, Fc gamma R cross-linking stimulated the release of AA from monocytes. Studies with selective inhibi tors revealed that the Fc gamma R-mediated activation of PLA(2) is dependen t on Ca2+ and tyrosine kinase activity. Together these results indicate a k ey role for PLA(2)/AA, but not its major metabolites, in mediating the Fc g amma R-stimuiated intracellular killing of S. aureus by monocytes.