Inhibition of Neutrophil Phospholipase A2 by p-Bromophenylacyl Bromide, Nordihydroguaiaretic Acid, 5,8,11,14-Eicosatetrayenoic Acid and Quercetin

Abstract

The lipoxygenase and/or cyclooxygenase inhibitors nordihydroguaiaretic acid (NDGA), 4,8,11 14-eicosatetrayenoic acid (ETYA) and the bioflavonoid, quercetin, also inhibit phospholipase A₂ (phosphatidase 2-acyl hydrolase; EC 3.1.1.4) activity of neutrophil acid extracts and sonicates. The IC₅₀ are 13 μM for NDGA, 22 μM for ETYA, and 100 μM for quercetin when measured on the neutrophil acid extracts; the IC₅₀ obtained with the sonicates are 11 μM, 12 μM and 57 μM, respectively. p-Bromophenylacyl bromide (BPB) inhibits the phospholipase A₂ activity of neutrophil acid extracts with an IC₅₀ of 10 μM. In contrast, intact neutrophils incubated for up to 1 h with BPB, washed to remove the drug, and sonicated to expose the phospholipase A₂, lose less than 20% of their activity. This strongly suggests that BPB does not inhibit neutrophil function by preventing phospholipase action.