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Priming by tumor necrosis factor‐α of human neutrophil NADPH‐oxidase activity induced by anti‐proteinase‐3 or anti‐myeloperoxidase antibodies
Author(s) -
Reumaux Dominique,
Hordijk Peter L.,
Duthilleul Patrick,
Roos Dirk
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0304144
Subject(s) - myeloperoxidase , biology , respiratory burst , tumor necrosis factor alpha , proteinase 3 , nadph oxidase , antibody , priming (agriculture) , microbiology and biotechnology , immunology , inflammation , reactive oxygen species , botany , germination
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 β 2 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 gp91 phox , the main component of the NADPH oxidase with β 2 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.