INHIBITION OF N-FORMYLMETHIONYL-LEUCYL-PHENYLALANINE-STIMULATED TYROSINE PHOSPHORYLATION AND PHOSPHOLIPASE-D ACTIVATION BY QUERCETIN IN RABBIT NEUTROPHILS

We investigated the effect of bioflavonoid quercetin on tyrosine phosp horylation and phospholipase D (PLD, EC 3.1.4.4) activation in rabbit peritoneal neutrophils stimulated by N-formylmethionyl-leucylphenylala nine (fMLP). The quercetin dose-dependently inhibited degranulation an d superoxide production in fMLP stimulated neutrophils. A strong inhib itory effect of quercetin on the tyrosine phosphorylation of several p roteins (40, 42, 43, 45, 46 and 75 kDa) was observed when the neutroph ils were pretreated with different concentrations of quercetin. Furthe rmore, quercetin inhibited mitogen activated protein kinase (MAP kinas e) and PLD activation induced by fMLP in a dose-dependent manner. The reduction in PLD activity was 30% at 0.1 mu M and 70% at 100 mu M of q uercetin. These results suggest that impairment of neutrophil function s by quercetin may be due, at least in part, to inhibition of tyrosine phosphorylation and PLD activation. (C) 1997 Elsevier Science Inc.