LIDOCAINE INHIBITS PRIMING AND PROTEIN-TYROSINE PHOSPHORYLATION OF HUMAN PERIPHERAL NEUTROPHILS

The addition of agents, such as tumor necrosis factor-alpha, to human peripheral neutrophils (HPPMN) induces priming, which enhances the rec eptor-mediated superoxide (O2-) generation and tyrosine phosphorylatio n of several HPPMN proteins. Lidocaine, a local anesthetic, inhibited both enhanced O2- generation and tyrosine phosphorylation of a 115 kDa protein in a concentration- and time-dependent manner. Lidocaine also inhibited protein kinase C sensitive O2- generation induced by phorbo l myristate acetate, but not time dependently. Furthermore, lidocaine inhibited O2- generation by non-primed HPPMN induced by formylmethiony l-leucyl-phenylalanine, but this inhibition needed a higher concentrat ion of lidocaine compared with that of primed HPPMN. These results sug gest that lidocaine inhibits the priming step of neutrophil activation and that it is linked to the inhibition of tyrosine phosphorylation o f a 115 kDa protein.