Human polymorphonuclear neutrophil activation with arachidonic acid.
The capacity of arachidonic acid (AA) to stimulate granule exocytosis from human polymorphonuclear neutrophils (PMNs) was investigated. AA induced the selected extracellular release of azurophil (myeloperoxidase, lysozyme) and specific (lysozyme, vitamin B12 binding protein) granule constituents from human PMNs in a time- and concentration-dependent manner. Cytochalasin B (CB) enhanced but was not required for PMN activation with AA. Although extracellular calcium had no effect on granule exocytosis, AA did stimulate the mobilization of intracellular sequestered Ca2+ which resulted in an increase in cytosolic-free Ca2+ ([Ca2+]i) as reflected by increased fluorescence of Fura-2-treated cells. AA stimulated Ca2+/phospholipid-dependent protein kinase C (PK-C) activity in PMNs. 4,4'-Diisothiocyano-2,2'-disulphonic acid stilbene (DIDS), an anion channel blocker, caused a concentration-dependent inhibition of granule enzyme release. Activation of PMNs with AA was unaffected by the lipoxygenase/cycle-oxygenase inhibitors, 5,8,11, 14-eicosatetraynoic acid (ETYA) and benoxaprofen, a lipoxygenase inhibitor, 6, 9, deepoxy-6,9-(phenylimino) delta 6,8-prostaglandin 1(1) (piriprost potassium) or a pure cyclo-oxygenase inhibitor, flurbiprofen. These data define the properties of AA as a secretory stimulus for human PMNs.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001572:Benzofurans; D002118:Calcium / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology; D005453:Fluorescence; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000302:isolation & purification
D001095:Arachidonic Acids; D001572:Benzofurans; D005227:Fatty Acids; D005456:Fluorescent Dyes; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D016718:Arachidonic Acid; D003571:Cytochalasin B; D011493:Protein Kinase C; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D016257:Fura-2