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Cryptic O2- -generating NADPH oxidase in dendritic cells.
Sylvie Elsen1, Jacques Doussière, Christian L Villiers
1Laboratoire de Biochimie et Biophysique des Systèmes Intégrés (UMR 5092 CNRS-CEA-UJF), Département Réponse et Dynamique Cellulaires, CEA-Grenoble, Grenoble Cedex, France.
Journal of Cell Science
|May 6, 2004
Summary
Dendritic cells (DCs) possess a cryptic NADPH oxidase enzyme. This enzyme
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Neutrophils utilize NADPH oxidase for superoxide (O2-) generation.
- Dendritic cells (DCs) possess NADPH oxidase components but show limited O2- production.
- Pro-inflammatory stimuli enhance O2- generation in DCs.
Purpose of the Study:
- To investigate the reasons for the suppressed respiratory burst in dendritic cells (DCs).
- To identify mechanisms controlling NADPH oxidase activation in DCs.
- To understand how DCs respond to microbial stimuli via O2- production.
Main Methods:
- Immunodetection of NADPH oxidase components in murine DCs.
- Assessment of O2- generation in DCs stimulated with PMA and pro-inflammatory ligands.
- Cell-free systems using DC membranes and neutrophil oxidase for activation studies.
- Treatment of DC membranes with beta-octylglucoside (beta-OG), proteinase K, and heat.
Main Results:
- DCs exhibit immunodetectable NADPH oxidase components but a weak response to PMA alone.
- Preincubation with pro-inflammatory ligands significantly enhances PMA-induced O2- production in DCs.
- A membrane-bound inhibitory factor in DCs prevents NADPH oxidase activation.
- This inhibitor is protein in nature, sensitive to beta-OG treatment, and blocks neutrophil oxidase activation.
Conclusions:
- The NADPH oxidase in DCs is 'cryptic' due to a membrane-bound protein inhibitor.
- Pro-inflammatory ligands, mimicking microbial exposure, relieve this inhibition.
- This regulated O2- production likely contributes to DC's role in innate immunity.