Activation of phospholipase C is not correlated to the formation of prostaglandins and superoxide in cultured rat liver macrophages.
This study evaluates the role of inositol phosphates as possible mediators of the activation of phospholipase A2 and NADPH oxidase in cultured rat liver macrophages. Inositol phosphate formation was achieved by zymosan, immune complexes, latex particles and calcium ionophore while the release of arachidonic acid and the formation of prostaglandin E2 was also elicited by phorbol ester and NaF, but not by latex particles; generation of superoxide was obtained by zymosan and phorbol ester only. The kinetics of the formation of inositol phosphates revealed that within the first few minutes after zymosan addition inositol trisphosphate was formed, followed by inositol bisphosphate and inositol monophosphate. Pre-treatment of the cells with dexamethasone or removal of extracellular calcium led to an inhibition of the zymosan-induced formation of inositol phosphates and prostaglandin E2 but had no effect on the generation of superoxide; inhibition of the Na+/H+ exchanger by removal of extracellular sodium ions led to a decrease of the zymosan-induced synthesis of prostaglandin E2, but did not affect the formation of inositol phosphates and superoxide. Pre-treatment of the cells with phorbol ester decreased the zymosan-induced synthesis of prostaglandin E2 and superoxide, but even enhanced the zymosan-induced formation of inositol phosphates. These data indicate that in cultured rat liver macrophages the formation of prostaglandins and superoxide cannot be correlated to an activation of phospholipase C.
Dieter
P
P
Institute of Molecular Cell Biology, Freiberg, F.R.G.
Schulze-Specking
A
A
Fitzke
E
E
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation; D007295:Inositol Phosphates / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D007295:Inositol Phosphates; D009097:Multienzyme Complexes; D010703:Phorbol Esters; D013481:Superoxides; D015054:Zymosan; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D015232:Dinoprostone