Priming by tumor necrosis factor-α of human neutrophil NADPH-oxidase activity induced by anti-proteinase-3 or anti-myeloperoxidase antibodies

Anti‐proteinase‐3 (anti‐PR3) or anti‐myeloperoxidase (anti‐MPO) antibodies are capable of activating human neutrophils primed by TNF‐α in vitro. We described previously the involvement of FcγRIIa and β2 integrins in this neutrophil activation. In the literature, the requirement of TNF priming has be...

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Bibliographic Details
Published in:Journal of leukocyte biology 2006-12, Vol.80 (6), p.1424-1433
Main Authors: Reumaux, Dominique, Hordijk, Peter L., Duthilleul, Patrick, Roos, Dirk
Format: Article
Language:English
Subjects:
ANCA
Antibodies - immunology
Antibodies - pharmacology
Antigens, CD - immunology
Antigens, CD - metabolism
Bridged-Ring Compounds - pharmacology
CD18 Antigens - immunology
CD18 Antigens - metabolism
Cells, Cultured
Cytochalasins - pharmacology
Cytoskeleton - immunology
Cytoskeleton - metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Enzymologic - immunology
Humans
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - immunology
Myeloblastin - antagonists & inhibitors
Myeloblastin - biosynthesis
Myeloblastin - immunology
NADPH Oxidase 2
NADPH Oxidases - biosynthesis
NADPH Oxidases - immunology
neutrophil activation
Neutrophil Activation - drug effects
Neutrophil Activation - immunology
Neutrophils - enzymology
Neutrophils - immunology
Peroxidase - antagonists & inhibitors
Peroxidase - biosynthesis
Peroxidase - immunology
Phosphodiesterase Inhibitors - pharmacology
Receptors, IgG - immunology
Receptors, IgG - metabolism
Thiones - pharmacology
TNF‐α
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - pharmacology
Type C Phospholipases - antagonists & inhibitors
Type C Phospholipases - immunology
vasculitis
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Summary:Anti‐proteinase‐3 (anti‐PR3) or anti‐myeloperoxidase (anti‐MPO) antibodies are capable of activating human neutrophils primed by TNF‐α in vitro. We described previously the involvement of FcγRIIa and β2 integrins in this neutrophil activation. In the literature, the requirement of TNF priming has been attributed to an effect of TNF‐α on the expression of PR3 or MPO on the cell surface. Under our experimental conditions, TNF‐α (2 ng/ml) increased the binding of the antibody against PR3, whereas binding of the antibody against MPO could hardly be detected, not even after TNF‐α treatment. The aim of this study was to consider (an)other(s) role(s) for TNF‐α in facilitating the NADPH‐oxidase activation by these antibodies. We demonstrate the early mobilization of the secretory vesicles as a result of TNF‐induced increase in intracellular‐free calcium ions, the parallel colocalization of gp91phox, the main component of the NADPH oxidase with β2 integrins and FcγRIIa on the neutrophil surface, and the FcγRIIa clustering upon TNF priming. TNF‐α also induced redistribution of FcγRIIa to the cytoskeleton in a dose‐ and time‐dependent manner. Moreover, blocking CD18 MHM23 antibody, cytochalasin B, and D609 (an inhibitor of phosphatidylcholine phospholipase C) inhibited this redistribution and the respiratory burst in TNF‐treated neutrophils exposed to anti‐PR3 or anti‐MPO antibodies. Our results indicate direct effects of TNF‐α in facilitating neutrophil activation by these antibodies and further support the importance of cytoskeletal rearrangements in this priming process.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0304144