title: Postreceptor events associated with human neutrophil activation by interleukin-8.
abstract: Recombinant human monocyte-derived interleukin-8 (IL-8M), recombinant human endothelium-derived IL-8 (IL-8E), and a recombinant human truncated form of IL-8 (IL-8T) stimulated a time-dependent (t 1/2 approximately 2-3 s) and concentration-dependent (0.1-100 nM) release of azurophil (myeloperoxidase) and specific (vitamin B12 binding protein, gelatinase) granule constituents from cytochalasin B-treated human neutrophils (HNs) wherein IL-8T = IL-8M greater than IL-8E. An increase in the cytosolic free calcium concentration ([Ca2+]i) was greater in IL-8T- than in IL-8M- or IL-8E-activated HNs, and IL-8T was more potent than either IL-8M or IL-8E in sequentially desensitizing the HNs to the effects of the other IL-8 forms. IL-8 induced a time- and concentration-dependent (0.1-100 nM) increase in the production of inositol 1,4,5-trisphosphate (IP3) in HNs. U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione), a potent inhibitor of phospholipase C-catalyzed events in HNs, suppressed IL-8-triggered IP3 production, increased [Ca2+]i and granule exocytosis in HNs. The membrane-associated activity of the alpha and beta subtypes of protein kinase C was significantly enhanced in IL-8-activated cells.
authors.affiliation: Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: L M
authors.initials: LM
authors.lastname: Sam
authors.forename: K L
authors.initials: KL
authors.lastname: Leach
authors.forename: J M
authors.initials: JM
authors.lastname: Justen
mesh_terms: D000906:Antibodies; D016718:Arachidonic Acid / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D005089:Exocytosis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D016209:Interleukin-8 / Q000494:pharmacology*; D007527:Isoenzymes / Q000276:immunology; D007536:Isomerism; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis / Q000276:immunology; D011760:Pyrrolidinones / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology*; D023062:Receptors, Interleukin-8A; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000906:Antibodies; D016227:Benzoquinones; D004963:Estrenes; D016209:Interleukin-8; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D011760:Pyrrolidinones; D011971:Receptors, Immunologic; D023062:Receptors, Interleukin-8A; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D007975:Leukotriene B4; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium