Arachidonic acid, but not its metabolites, is essential for FcγR‐stimulated intracellular killing of Staphylococcus aureus by human monocytes

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Abstract
Since arachidonic acid (AA) production by phospholipase A2 (PLA2) is essential for the Fcγ receptor (FcγR)‐mediated respiratory burst and phagocytosis of opsonized erythrocytes by monocytes and macrophages, we focused in this study on the role of AA and its metabolites in the FcγR‐stimulated intracellular killing of Staphylococcus aureus by human monocytes. The results revealed that the PLA2 inhibitors, but not inhibitors of cyclo‐oxygenase and lipoxygenase, markedly suppressed the FcγR‐mediated killing process. The production of O−2 by monocytes upon FcγR cross‐linking was inhibited by 4‐bromophenacyl bromide in a dose‐dependent fashion, indicating that inhibition of PLA2 activity impairs the oxygen‐dependent bactericidal mechanisms of monocytes, which could be partially restored by addition of exogenous AA and docosahexaenoic acid, but not myristic acid. These polyunsaturated fatty acids, but not myristic acid, stimulated the intracellular killing of S. aureus by monocytes, although not as effectively as FcγR cross‐linking. Furthermore, FcγR cross‐linking stimulated the release of AA from monocytes. Studies with selective inhibitors revealed that the FcγR‐mediated activation of PLA2 is dependent on Ca2+ and tyrosine kinase activity. Together these results indicate a key role for PLA2/AA, but not its major metabolites, in mediating the FcγR‐stimulated intracellular killing of S. aureus by monocytes.

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