Abstract
The tyrosine kinase inhibitors erbstatin and herbimycin A inhibited the chemotactic response and the superoxide anion (O-2) production stimulated by FMLP in human polymorphonuclear leukocytes (PMN) in similar manners. These compounds also inhibited phospholipase D (PLD) -catalysed breakdown of phosphatidyl choline, suggesting a possible link between tyrosine kinase and PLD. In the presence of propranolol (phosphatidic acid (PA) phosphohydrolase inhibitor), or ethanol, the activation of PLD results in the modulation of PA and/or diglyceride (DG) generation, producing an irregularity in O-2 production. However, PMN motility was not affected in these conditions.
These results suggest that PLD is a downstream effector of FMLP-induced tyrosine kinase activation that leads to activation of the PMN superoxide release but not to chemotactic migration. In contrast, the tyrosine kinase inhibitors did not inhibit inositol 1, 4, 5-triphosphate generation and increase of intracellular concentration of free calcium. These results support the premise that there are divergent signaling pathways for activations of distinct enzymes and functions in PMN. This premise has been proved by the recent renewed appreciation for the complexities of chemoattractant signaling pathways.
