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Published online before print September 22, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0304144

Received for publication March 6, 2004.
Revised July 31, 2006.
Accepted for publication August 10, 2006.

Article

Priming by tumor necrosis factor- of human neutrophil NADPH-oxidase activity induced by antiproteinase-3 or antimyeloperoxidase antibodies

Dominique Reumaux ^*@, Peter L. Hordijk , Patrick Duthilleul ^*, and Dirk Roos

*Département d’Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, and Laboratoire d’Hématologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille-2, France; and Sanquin Research at Central Laboratory for Blood Transfusion (CLB) and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands

^@ To whom correspondence should be addressed. E-mail: dominique.reumaux{at}libertysurf.fr.

	Abstract

Antiproteinase-3 (anti-PR3) or antimyeloperoxidase (anti-MPO) antibodies are capable of activating human neutrophils primed by TNF- in vitro. We described previously the involvement of FcRIIa and ₂-integrins in this neutrophil activation. In the literature, the requirement of TNF priming has been attributed to an effect of TNF- on the expression of PR3 or MPO on the cell surface. Under our experimental conditions, TNF- (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- treatment. The aim of this study was to consider (an)other(s) role(s) for TNF- in facilitating the NADPH-oxidase activation by these antibodies. We demonstrate the early mobilization of the secretory vesicles as a result of a TNF-induced increase in intracellular-free calcium ions, the parallel colocalization of gp91^phox, the main component of the NADPH oxidase with ₂-integrins and FcRIIa on the neutrophil surface, and the FcRIIa clustering upon TNF priming. TNF- also induced redistribution of FcRIIa 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- in facilitating neutrophil activation by these antibodies and further support the importance of cytoskeletal rearrangements in this priming process.

Key Words: TNF- • neutrophil activation • ANCA • vasculitis

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