Possible role of arachidonic acid and of phospholipase A2 in the control of lysosomal enzyme release from human polymorphonuclear leukocytes.
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.
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
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