Cryptic O2–-generating NADPH oxidase in dendritic cells
| Autor: | Sylvie Elsen, Anne Papaioannou, Patrice N. Marche, Rolande Berthier, Pierre V. Vignais, Jacques Doussiere, Mathias Faure, Nathalie Grandvaux, Christian L. Villiers |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Cytoplasm Lipopolysaccharide Neutrophils Heterologous Heme Biology Mice chemistry.chemical_compound Glucosides Superoxides Animals Enzyme Inhibitors Cells Cultured Mice Inbred BALB C Oxidase test Membrane Glycoproteins NADPH oxidase Cell Membrane NADPH Dehydrogenase Membrane Transport Proteins NADPH Oxidases Dendritic Cells Cell Biology Cytochromes b Phosphoproteins Proteinase K Respiratory burst Cell biology Enzyme Activation Cytosol chemistry Biochemistry Polyinosinic:polycytidylic acid NADPH Oxidase 2 biology.protein Tetradecanoylphorbol Acetate Cattle Inflammation Mediators Reactive Oxygen Species |
| Zdroj: | Journal of Cell Science. 117:2215-2226 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | All the components of the O(2)(-)-generating NADPH oxidase typically found in neutrophils, namely a membrane-bound low potential flavocytochrome b and oxidase activation factors of cytosolic origin, are immunodetectable in murine dendritic cells (DCs). However, in contrast to neutrophils, DCs challenged with phorbol myristate acetate (PMA) can barely mount a significant respiratory burst. Nevertheless, DCs generate a substantial amount of O(2)(-) in the presence of PMA following preincubation with pro-inflammatory ligands such as lipopolysaccharide and pansorbin, and to a lesser extent with anti-CD40 or polyinosinic polycytidylic acid. We found that the virtual lack of the oxidase response to PMA alone is specifically controlled in DCs. Through the use of homologous and heterologous cell-free systems of oxidase activation, we showed the following: (1) a NADPH oxidase inhibitory factor is located in DC membranes; it exerts its effect on oxidase activation and not on the activated oxidase. (2) The inhibition is relieved by pretreatment of DC membranes with beta-octylglucoside (beta-OG). (3) The beta-OG-extracted inhibitory factor prevents the activation of neutrophil oxidase. (4) The inhibitory activity is lost after treatment of DC membranes with proteinase K or heating, which points to the protein nature of the inhibitory factor. Overall, these data indicate that the O(2)(-)-generating oxidase in DCs is cryptic, owing to the presence of a membrane-bound inhibitor of protein nature that prevents oxidase activation. The inhibition is relieved under specific conditions, including a prolonged contact of DCs with pro-inflammatory ligands from microbial origin, allowing a substantial production of O(2)(-), which may contribute to the response of DCs to a microbial exposure. |
| Databáze: | OpenAIRE |
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