Inhibition of polymorphonuclear leukocyte oxidative metabolism by exogenous phospholipase C

Abstract

We studied the effects of exogenous, purified phospholipase C (PLC) on neutrophil oxidative metabolism, lysosomal enzyme release and aggregation. We found that PLC inhibited O 2 − and H 2O 2 generation and oxygen consumption, but did not alter glucose oxidation via the hexose monophosphate shunt. In contrast, we found a striking stimulation of aggregation and release of the lysosomal enzymes lysozyme and β-glucuronidase. In experiments designed to further characterize the mechanism of the PLC effect on membrane activation we studied the effect of PLC on intracellular calcium concentration [Ca 2+] i and found that PLC did not interfere with the fMLP-mediated rise in [Ca 2+] i, suggesting that its inhibitory effect on the respiratory burst does not involve inhibition of early signal transduction events. In addition, we found that PLC alone results in mobilization of intracellular Ca 2+ stores, consistent with its stimulatory effect on aggregation and lysosomal enzyme release.