Interleukin-1 stimulates granule exocytosis from human neutrophils.
The interaction of human polymorphonuclear neutrophilic leukocytes (neutrophils) with interleukin-1 (IL-1) resulted in a time- and concentration-dependent, selective, release of azurophil (myeloperoxidase, lysozyme) and specific (lysozyme, vitamin B12-binding protein) granule constituents. Myeloperoxidase (MPO) and lysozyme secretion was markedly attenuated if neutrophils were not exposed to cytochalasin B (CB) prior to contact with IL-1. Degranulation was significantly enhanced in the presence of extracellular calcium. IL-1-elicited granule exocytosis was inhibited by the intracellular calcium antagonist, 8-(N,N-diethylamino)-octyl-(3,4,5-trimethoxy) benzoate hydrochloride (TMB-8), a calmodulin antagonist, trifluoperazine (TFP), and an anion channel blocker, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). An evaluation of the role of arachidonic acid metabolites in IL-1-induced neutrophil activation revealed a suppressive effect on enzyme release exerted by the lipoxygenase inhibitors, piriprost potassium (6,9,deepoxy-6,9-(phenylimino)-delta 6,8 -prostaglandin I1, U-60,257B) and NDGA (nordihydroguaiaretic acid), and a cyclooxygenase/lipoxygenase inhibitor, ETYA (5,8,11,14-eicosatetraynoic acid). These data describe the characteristics of IL-1 as a human neutrophil secretagogue, and enhance our insight into the mechanism of inflammatory cell activation with this monokine.
R J
RJ
Smith
B J
BJ
Bowman
S C
SC
Speziale
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D003847:Deoxyglucose / Q000494:pharmacology / Q000031:analogs & derivatives; D005089:Exocytosis / Q000187:drug effects*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007372:Interferons / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000648:ultrastructure; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
D000963:Antimetabolites; D001095:Arachidonic Acids; D002413:Cations, Divalent; D007375:Interleukin-1; D007376:Interleukin-2; D014268:Trifluoperazine; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D003571:Cytochalasin B; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D007372:Interferons; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D009113:Muramidase; C037904:6-deoxyglucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid