A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids.
When rabbit peritoneal neutrophils were treated with glucocorticoids, their chemotactic response to stimulation by the chemoattractant fMet-Leu-Phe was markedly reduced. Preincubation of cells with glucocorticoids also decreased phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) activity in situ as measured by the release of [1-14C]arachidonic acid previously incorporated into phospholipids. The inhibitory potencies of glucocorticoids on phospholipase A2 activity correlated well with their anti-inflammatory activities and their abilities to bind to glucocorticoid receptors. Inhibitors of RNA and protein synthesis suppressed the inhibitory effect of glucocorticoids on phospholipase A2 activity. Digestion of the glucocorticoid-treated cells by Pronase overcame the inhibitory activity. Phospholipase A2 activity induced by Ca2+ ionophore A23187 was not affected by Pronase treatment. Gel filtration of proteins from neutrophil membranes labeled with [3H]lysine showed an induction of protein(s) (about 40,000 daltons) after glucocorticoid treatment. This protein inhibited a partially purified pancreatic phospholipase A2 and reduced the peptide-initiated chemotactic response of neutrophils.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000096:biosynthesis; D005938:Glucocorticoids / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D010743:Phospholipids; D012333:RNA, Messenger; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2