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NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils

Item Type:Article
Title:NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils
Creators Name:von Vietinghoff, S., Tunnemann, G., Eulenberg, C., Wellner, M., Cardoso, M.C., Luft, F.C. and Kettritz, R.
Abstract:Anti-neutrophil cytoplasmic antibodies (ANCA) 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 HEK 293 and HL60 cell lines. Using neutrophils from healthy donors, vasculitis patients, 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 absent in a patient with paroxysmal nocturnal hemoglobinuria. PR3 and NB1 co-immunoprecipitated from and colocalised 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.
Keywords:Proteinase 3, NB1, Neutrophils, ANCA-associated vasculitis, Antineutrophil Cytoplasmic Antibodies, Surface Antigens, Cell Membrane, Cultured Cells, Fetal Blood, Glycosylphosphatidylinositols, Hematopoietic Stem Cells, Immunoprecipitation, Isoantigens, Membrane Glycoproteins, Myeloblastin, Neutrophils, Cell Surface Receptors, Transfection
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology
Volume:109
Number:10
Page Range:4487-4493
Date:15 May 2007
Official Publication:https://doi.org/10.1182/blood-2006-10-055327
PubMed:View item in PubMed

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