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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4487-4493. Prepublished online as a Blood First Edition Paper on January 23, 2007; DOI 10.1182/blood-2006-10-055327. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-055327v1 109/10/4487    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by von Vietinghoff, S. Articles by Kettritz, R. Search for Related Content PubMed PubMed Citation Articles by von Vietinghoff, S. Articles by Kettritz, R. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils Sibylle von Vietinghoff1, Gisela Tunnemann2, Claudia Eulenberg1, Maren Wellner1, M. Cristina Cardoso2, Friedrich C. Luft1,2, and Ralph Kettritz1 1 Franz Volhard Clinic, Department of Nephrology and Hypertension, Medical Faculty of the Charité, HELIOS-Klinikum, Berlin, Germany; 2 Max-Delbrück Center for Molecular Medicine, Berlin, Germany Antineutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase 3 (PR3) are central to a form of ANCA-associated vasculitis. Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils. Neutrophils were isolated from patients and healthy controls, and hematopoietic stem cells from cord blood served as a model of neutrophil differentiation. Surface expression was analyzed by flow cytometry and confocal microscopy, and proteins were analyzed by Western blot experiments. Neutrophil subsets were separated by magnetic cell sorting. Transfection experiments were carried out in HEK293 and HL60 cell lines. Using neutrophils from healthy donors, patients with vasculitis, and neutrophilic differentiated stem cells we found that mPR3 display was restricted to cells expressing neutrophil glycoprotein NB1, a glycosylphosphatidylinositol (GPI)–linked surface receptor. mPR3 expression was decreased by enzymatic removal of GPI anchors from cell membranes and was absent in a patient with paroxysmal nocturnal hemoglobinuria. PR3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. Transfection with NB1 resulted in specific PR3 surface binding in different cell types. We conclude that PR3 membrane expression on neutrophils is mediated by the NB1 receptor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Brachemi, A. Mambole, F. Fakhouri, L. Mouthon, L. Guillevin, P. Lesavre, and L. Halbwachs-Mecarelli Increased Membrane Expression of Proteinase 3 during Neutrophil Adhesion in the Presence of Anti Proteinase 3 Antibodies J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2330 - 2339. [Abstract] [Full Text] [PDF]

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