title: Possible role of arachidonic acid and of phospholipase A2 in the control of lysosomal enzyme release from human polymorphonuclear leukocytes.
abstract: We have studied the role of arachidonic acid (AA) metabolism in the release of lysosomal enzymes (beta-glucuronidase and lysozyme) from human polymorphonuclear leukocytes (PMNs). 5,8,11,14-Eicosatetraenoic acid (ETYA), which inhibits both the cyclo-oxygenase and the lipoxygenase pathways of AA metabolism, was found to cause a dose-dependent inhibition of lysosomal enzyme release from human PMNs induced by immunological (i.e., serum-treated zymosan: Zx) and nonimmunological stimuli (i.e., formyl methionine-containing peptide and the Ca2+ ionophore A23187). In contrast, the non-steroidal anti-inflammatory drugs (indomethacin, meclofenamic acid and aspirin), which only block the cyclo-oxygenase pathway of AA metabolism, had little effect on enzyme release from PMNs induced by the same stimuli. 5,8,11-Eicosatriynoic acid (ETI), a selective inhibitor of the lipoxygenase pathway of AA metabolism, caused a dose-dependent inhibition of lysosomal enzyme release elicited by Zx, f-met peptide, and A23187. p-Bromophenacyl bromide (BPB), which inhibits the phospholipase A2 (PLA2) activity in several tissues, was found to cause a dose-dependent inhibition of lysosomal enzyme release induced by the same immunological and non-immunological stimuli. The inhibitory effect of BPB on enzyme release was irreversible and extremely rapid. It appears that activation of PLA2 and the products of the AA metabolism, generated via a lipoxygenase pathway, play an essential role in the biochemical control of human PMNs activation and secretion.
mesh_terms: D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000098:Acetophenones / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology*; D009113:Muramidase / Q000097:blood; D009504:Neutrophils / Q000378:metabolism*; D010740:Phospholipases / Q000097:blood*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2
chemical_list: D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D015117:5,8,11,14-Eicosatetraynoic Acid; C026603:5,8,11-eicosatriynoic acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D009113:Muramidase; D005966:Glucuronidase; C006821:4-bromophenacyl bromide