Neutrophil-degranulating action of 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine. Comparison with other degranulating agents.
5,12-Dihydroxy-6,8,10,14-eicosatetraenoic acid was prepared from rabbit neutrophils challenged with ionophore A23187 plus arachidonic acid. It was purified by reverse-phase high-performance liquid chromatography with the use of a two-step procedure that effectively resolved the lipid from closely eluting contaminants. The phospholipid 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine was prepared from beef heart plasmalogen. Confirming earlier reports, both lipids stimulated human polymorphonuclear neutrophils to release granule-bound enzymes. Their respective degranulating actions took less than 5 minutes to become maximal, were dependent upon the presence of cytochalasin B, and required intact pathways of arachidonic acid metabolism, as judged by the inhibitory actions of arachidonate antimetabolites. Neither lipid required more than trace concentrations of extracellular calcium to effect optimal amounts of enzyme release. In one or more of these regards the two lipids differed strikingly from other neutrophil-degranulating agents such as A23187, N-formyl-methionyl-leucyl-phenylalanine, and phorbol myristate acetate. The mechanism of action of the two lipid stimuli, therefore, appear to differ somewhat from the mechanisms of the other three stimuli.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002630:Chemotactic Factors / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D010972:Platelet Activating Factor; D011817:Rabbits; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D008244:Lysophosphatidylcholines; D009842:Oligopeptides; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D003571:Cytochalasin B; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium