Inhibition of polymorphonuclear leukocyte oxidative metabolism by exogenous phospholipase C.
We studied the effects of exogenous, purified phospholipase C (PLC) on neutrophil oxidative metabolism, lysosomal enzyme release and aggregation. We found that PLC inhibited O2- and H2O2 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 beta-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 [Ca2+]i and found that PLC did not interfere with the fMLP-mediated rise in [Ca2+]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 Ca2+ stores, consistent with its stimulatory effect on aggregation and lysosomal enzyme release.
Gordon
L I
LI
Northwestern University, Department of Medicine, Chicago, Illinois 60611.
Schmeichel
C
C
Prachand
S
S
Weitzman
S A
SA
D002118:Calcium / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D006600:Hexosephosphates / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D013481:Superoxides / Q000378:metabolism; D010738:Type C Phospholipases / Q000494:pharmacology*
D006600:Hexosephosphates; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D010738:Type C Phospholipases; D010100:Oxygen; D002118:Calcium