Signal Transduction and Priming of Human Neutrophils

Preincubation of human polymorphonuclear neutrophils (PMN) with diverse cytokines for 15 s enhanced the subsequent formyl-Met-Leu-Phe (FMLP)- induced leukotriene (LT) generation. These results correlated with a significant enhanced GTPase activity and an additive actin polymerization. Preincubation with genistein, an inhibitor of tyrosine kinases, inhibited LT formation as well as GTPase activities. Incubation with IL-3 or 11-3 and FMLP led to a shift in [35S]-γ-GTP binding to microsomal proteins as compared to unstimulated or FMLP-stimulated PMN. These results suggest a fundamental role of low molecular weight GTP-binding proteins and tyrosine kinases for cellular activation.