Src-family kinase-p53/56(lyn) plays an important role in TNF alpha-stimulated production of O-2(-) by human neutrophils adherent to fibrinogen

Stimulation of neutrophil function by TNF alpha is largely dependent on bet a(2) integrins. It has also been proposed that src-family kinases are invol ved in this process. However, the functions of src-like kinases in human ne utrophils 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 pla y in TNF alpha stimulation of neutrophil function. Our results demonstrated that, in neutrophils adherent to fibrinogen, PP1 inhibited TNF alpha-stimu lated superoxide production and protein tyrosine phosphorylation ina dose-d ependent manner. In in vitro kinase assays, PPI profoundly inhibited the ac tivation of p53/56(lyn) but not p59(hck) or p72(syk). Only slight inhibitio n was found of p58(c-fgr) These data indicate that p53/56(lyn) plays an imp ortant role in TNF alpha-mediated stimulation of PMN function.