Src-family kinase-p53/ Lyn p56 plays an important role in TNF-alpha-stimulated production of O2- by human neutrophils adherent to fibrinogen.

Stimulation of neutrophil function by TNFalpha is largely dependent on beta2 integrins. It has also been proposed that src-family kinases are involved in this process. However, the functions of src-like kinases in human neutrophils still remain to be determined. In the present study, we used the new src-family kinase specific inhibitor PP1 [4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] to investigate the role src-kinases play in TNFalpha stimulation of neutrophil function. Our results demonstrated that, in neutrophils adherent to fibrinogen, PP1 inhibited TNFalpha-stimulated superoxide production and protein tyrosine phosphorylation in a dose-dependent manner. In in vitro kinase assays, PP1 profoundly inhibited the activation of p53/56lyn but not p59hck or p72syk. Only slight inhibition was found of p58c-fgr. These data indicate that p53/56lyn plays an important role in TNFalpha-mediated stimulation of PMN function.