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Keywords:

  • Cellular activation;
  • Immune regulation;
  • Innate immunity;
  • Neutrophils

Peroxiredoxin 6-phospholipase A2 (Prdx6-PLA2) is a bi-functional enzyme with peroxi-redoxin (Prdx) and phospholipase A2 (PLA2) activities. To investigate its impact on phagocyte NADPH oxidase (phox) activity in a neutrophil model, the protein was knocked down in PLB-985 cells using stable expression of a small hairpin RNA (shRNA) and phox activity was monitored after cell differentiation. The knockdown cells had reduced oxidase activity in response to stimulation with the formylated peptide fMLF, but the response to the phorbol ester PMA was unchanged. Reintroduction of shRNA-resistant Prdx6-PLA2 into the knockdown cells by stable transfection with a Prdx6-PLA2 expression plasmid restored the fMLF response, as did reintroduction of Prdx6-PLA2 mutated in the Prdx active site; reintroduction of PLA2 active site mutants, however, failed to restore the response. Thus, the PLA2 activity of Prdx6-PLA2 in intact cells mediates its ability to enhance phox activity in response to fMLF. In combination with previous publications by other groups, our work indicates that various PLA2 isoforms can enhance oxidase activity but they are differentially important in different cell types and in the response to different agonists.