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 receptor-mediated superoxide (O2-) generation and tyrosine phosphorylation 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 phorbol myristate acetate, but not time dependently. Furthermore, lidocaine inhibited O2- generation by non-primed HPPMN induced by formylmethionyl-leucyl-phenylalanine, but this inhibition needed a higher concentration of lidocaine compared with that of primed HPPMN. These results suggest that lidocaine inhibits the priming step of neutrophil activation and that it is linked to the inhibition of tyrosine phosphorylation of a 115 kDa protein.
Department of Anesthesiology and Resuscitology, Kochi Medical School, Japan.
T
T
Kanbara
M K
MK
Tomoda
E F
EF
Sato
W
W
Ueda
M
M
Manabe
D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008012:Lidocaine; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate