Effects of non-steroidal anti-inflammatory drugs on human neutrophil NADPH oxidase in both whole cell and cell-free systems.

The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the respiratory burst oxidase (NADPH oxidase, EC 1.6.99.6) from human neutrophils in both whole cell and fully soluble (cell-free) systems were investigated. Three NSAIDs, indomethacin, salicylic acid and acetylsalicylic acid (aspirin), were found to inhibit the superoxide generation by human neutrophils exposed to phorbol myristate acetate in a whole cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in a cell-free system. Concentrations of these NSAIDs required for 50% inhibition of the oxidase (IC50) were: indomethacin (180 microM in both systems), salicylic acid (1.30 mM in the cell-free system, and more than 3.0 mM in the whole cell system) and acetylsalicylic acid (1.35 mM in the cell-free system, and more than 3.0 mM in the whole cell system). In addition, in the cell-free system, these NSAIDs did not change the Km values for NADPH of the oxidase. These results suggest that these NSAIDs, especially indomethacin, concentration-dependently inhibit the reconstitution of the solubilized membrane-bound enzyme by sodium dodecyl sulfate in the cell-free system.