Tumor necrosis factor stimulates human neutrophils to release leukotriene B4 and platelet-activating factor. Induction of phospholipase A2 and acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine O2-acetyltransferase activity and inhibition by antiproteinase.
Tumor necrosis factor stimulates polymorphonuclearneutrophils to synthesize leukotriene B4 and platelet-activating factor (PAF), but alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin block this response. However, proteinases such as elastase and cathepsin G induce preferentially synthesis of PAF. An acetyltransferase required, together with phospholipase A2, in the remodeling pathway of PAF synthesis is activated in polymorphonuclearneutrophils stimulated by tumor necrosis factor and elastase. In contrast, 1-oleyl-2-acetylglycerol, a protein kinase C activator, promotes PAF formation by the de novo biosynthetic pathway without activating the acetyltransferase. Staurosporine, an inhibitor of protein kinase C, blocks PAF production apparently by inhibiting phospholipase A2. This suggests that diacylglycerols are involved in activating both pathway of PAF synthesis.
Camussi
G
G
Cattedra di Nefrologia Sperimentale, Dipartimento di Biochimica e Biofisica, 1 Facolta di Medicina, Università di Napoli, Italy.
Tetta
C
C
Bussolino
F
F
Baglioni
C
C
D000123:Acetyltransferases / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010587:Phagocytosis; D010740:Phospholipases / Q000096:biosynthesis*; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011480:Protease Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology
D010972:Platelet Activating Factor; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000514:alpha 1-Antichymotrypsin; D007975:Leukotriene B4; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D011494:Protein Kinases; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010196:Pancreatic Elastase