A purified lipocortin shares the anti-inflammatory effect of glucocorticosteroids in vivo in mice.
1. The injection of a suspension of a polyacrylamide gel (bio gel) into the dorsal subcutaneous area of mice induced an inflammatory reaction and the migration of neutrophils towards the inflamed site. 2. The intravenous administration of anti-inflammatory drugs (dexamethasone, indomethacin and lysine-acetylsalicylate) to polyacrylamide gel-treated mice inhibited the accumulation of neutrophils in the inflamed site. 3. A similar administration of a 36K mouse lipocortin, induced a strong dose-dependent inhibition of neutrophil accumulation in the inflamed site. 4. Dexamethasone and lipocortin inhibited the production of eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the inflamed site of polyacrylamide gel-treated mice. 5. Lipocortin impaired both phospholipase A2 (PLA2) activity and chemotaxis of isolated inflammatory neutrophils. 6. The present studies show an in vivo anti-inflammatory effect of lipocortin similar to that of glucocorticosteroids. In agreement with recent data on the extracellular effects of various lipocortins, these results might implicate lipocortin(s) in the anti-inflammatory effects of glucocorticosteroids.
Errasfa
M
M
Unité associée INSERM no. 285/Institut Pasteur, Paris, France.
Russo-Marie
F
F
D000818:Animals; D017302:Annexins; D000893:Anti-Inflammatory Agents; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology; D007958:Leukocyte Count; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010976:Platelet Count; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D017302:Annexins; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D002135:Calcium-Binding Proteins; D005938:Glucocorticoids; D016718:Arachidonic Acid; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2