Recombinant human monocyte IL-8 primes NADPH-oxidase and phospholipase A2 activation in human neutrophils. 1992

R H Daniels, and M J Finnen, and M E Hill, and J M Lackie
Yamanouchi Research Institute (U.K.), Littlemore Hospital, Oxford.

We demonstrate for the first time that recombinant human monocyte interleukin-8 (rhMIL-8) primes human neutrophil responses to fMLP. Human neutrophils preincubated for 10 min with 10(-8) M rhMIL-8 and then stimulated with micromolar fMLP show enhanced release of superoxide anions, platelet-activating factor (PAF) and arachidonic acid compared with cells which are not initially exposed to rhMIL-8. We also demonstrate that this enhancement of the neutrophil response is dependent on the dose of rhMIL-8 with the greatest enhancement corresponding with IL-8 levels which cause maximum shape change of neutrophils. Priming of neutrophils occurred after only 30 seconds preincubation with rhMIL-8 indicating that the mechanism of IL-8 priming is extremely rapid as was stimulation of neutrophil shape change by rhMIL-8. Priming of neutrophils with rhMIL-8 did not increase sensitivity to fMLP but enhanced responsiveness to activating concentrations. rhMIL-8 alone at levels used for priming caused no release of superoxide anions, arachidonic acid or PAF. These results suggest that IL-8 primes neutrophil phospholipase A2 and NADPH-oxidase activation in response to fMLP.

UI MeSH Term Description Entries
D009240 N-Formylmethionine Leucyl-Phenylalanine A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated. F-Met-Leu-Phe,N-Formyl-Methionyl-Leucyl-Phenylalanine,Formylmet-Leu-Phe,Formylmethionyl Peptide,Formylmethionyl-Leucyl-Phenylalanine,Formylmethionylleucylphenylalanine,N-Formylated Peptide,N-formylmethionyl-leucyl-phenylalanine,fMet-Leu-Phe,F Met Leu Phe,Formylmet Leu Phe,Formylmethionyl Leucyl Phenylalanine,Leucyl-Phenylalanine, N-Formylmethionine,N Formyl Methionyl Leucyl Phenylalanine,N Formylated Peptide,N Formylmethionine Leucyl Phenylalanine,N formylmethionyl leucyl phenylalanine,Peptide, Formylmethionyl,Peptide, N-Formylated,fMet Leu Phe
D009247 NADH, NADPH Oxidoreductases A group of oxidoreductases that act on NADH or NADPH. In general, enzymes using NADH or NADPH to reduce a substrate are classified according to the reverse reaction, in which NAD+ or NADP+ is formally regarded as an acceptor. This subclass includes only those enzymes in which some other redox carrier is the acceptor. (Enzyme Nomenclature, 1992, p100) EC 1.6. Oxidoreductases, NADH, NADPH,NADPH Oxidoreductases NADH,Oxidoreductases NADH, NADPH
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004306 Dose-Response Relationship, Immunologic A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell. Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016209 Interleukin-8 A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. CXCL8 Chemokine,Chemokine CXCL8,Chemotactic Factor, Macrophage-Derived,Chemotactic Factor, Neutrophil, Monocyte-Derived,IL-8,Neutrophil-Activating Peptide, Lymphocyte-Derived,Neutrophil-Activating Peptide, Monocyte-Derived,AMCF-I,Alveolar Macrophage Chemotactic Factor-I,Anionic Neutrophil-Activating Peptide,Chemokines, CXCL8,Chemotactic Factor, Neutrophil,Granulocyte Chemotactic Peptide-Interleukin-8,IL8,Monocyte-Derived Neutrophil Chemotactic Factor,Neutrophil Activation Factor,Alveolar Macrophage Chemotactic Factor I,Anionic Neutrophil Activating Peptide,CXCL8 Chemokines,CXCL8, Chemokine,Chemokine, CXCL8,Chemotactic Factor, Macrophage Derived,Chemotactic Peptide-Interleukin-8, Granulocyte,Granulocyte Chemotactic Peptide Interleukin 8,Interleukin 8,Lymphocyte-Derived Neutrophil-Activating Peptide,Macrophage-Derived Chemotactic Factor,Monocyte-Derived Neutrophil-Activating Peptide,Neutrophil Activating Peptide, Lymphocyte Derived,Neutrophil Activating Peptide, Monocyte Derived,Neutrophil Chemotactic Factor,Neutrophil-Activating Peptide, Anionic,Peptide, Anionic Neutrophil-Activating
D054467 Phospholipases A2 Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES. Lecithinase A2,Phospholipase A2

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