Characterization and pharmacological modulation of soluble phospholipase A2 generated during glycogen-induced rat peritonitis.
Soluble phospholipase A2 (PLA2) activity was assessed in rat peritoneal lavage fluid after an intraperitoneal injection of 6% glycogen. Enzyme activity immediately increased 5-fold above basal by 4 h. Activity decreased by only 30% at 18 h and remained at this elevated level through 72 h. The initial rise in PLA2 activity was coincident with protein extravasation but not with polymorphonuclear leukocyte infiltration, suggesting that the early PLA2 activity could be, in part, blood-derived. Mononuclear cell influx occurred later (4 h), peaked by 6-8 h but remained elevated through 72 h possibly contributing to the persistence of PLA2 activity through 20-72 h. The exudate PLA2 measured at 4-6 h (early) and 20-24 h (late), after glycogen administration, were biochemically compared. They were found to be neutral pH active, Ca(2+)-dependent and were similarly inhibited by the inhibitors, p-bromophenacylbromide, ellagic acid, gossypol and luffariellolide. Oral administration of dexamethasone to rats inhibited the appearance of PLA2 activity in the peritoneal lavage fluid as well as cellular influx and protein extravasation. Indomethacin had no effect on these parameters. These studies demonstrate that PLA2 is an integral component of glycogen-induced peritonitis and can be pharmacologically manipulated.
Marshall
L A
LA
Inflammation Pharmacology, Smithkline-Beecham Pharmaceuticals, King of Prussia, PA 19406.
Murphy
J
J
Marinari
L
L
Chang
J
J
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006003:Glycogen; D007213:Indomethacin / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar
D003907:Dexamethasone; D006003:Glycogen; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin