| Effect of anti-neutrophil cytoplasmic antibodies on proteinase 3-induced apoptosis of human endothelial cells. | |
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MedLine Citation:
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PMID: 9714408 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Wegener's granulomatosis is characterized by crescentic necrotizing glomerulonephritis and systemic vasculitis. Both proteinase 3 (PR3) and anti-neutrophil cytoplasmic antibodies (ANCA), directed against this enzyme, are thought to play a pathogenic role. PR3 has been shown to cause detachment and cytolysis of human umbilical vein endothelial cells (HUVEC) in vitro and to induce apoptosis of bovine pulmonary artery endothelial cells. In the present study we investigated the effect of PR3 and ANCA on the induction of apoptosis of human endothelial cells in vitro. HUVEC were cultured in the absence or presence of varying concentrations of PR3 for different time periods and apoptosis was assessed by three different methods. Staining of the cells with Hoechst 33258 and assessment of nuclear morphology by ultraviolet (UV) light microscopy revealed a dose-dependent induction of apoptosis, as determined by cell counts. A concentration of 8 microg/ml PR3 was found to induce 16% apoptosis after 16 h incubation. Analysis of apoptosis by flow cytometry using the terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL) method also demonstrated a dose-dependent induction of apoptosis by PR3. DNA fragmentation was confirmed by agarose gel electrophoresis. To investigate the effect of ANCA on PR3-mediated apoptosis, HUVEC were exposed to immunoglobulin G (IgG) from patients with Wegener's granulomatosis or systemic vasculitis, and from normal controls, in the presence or absence of PR3. Enhancement of PR3-mediated apoptosis was found in two of 10 IgG samples with anti-PR3 activity, whereas a reduction in apoptosis was observed in two others. Anti-MPO (myeloperoxidase)-positive IgG, six additional anti-PR3 positive IgG samples and control IgG samples did not have any detectable effect on apoptosis. These studies suggest that ANCA may modulate the relative degree of injury in some cases of Wegener's granulomatosis. |
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Authors:
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M E Taekema-Roelvink; C van Kooten; M C Janssens; E Heemskerk; M R Daha |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Scandinavian journal of immunology Volume: 48 ISSN: 0300-9475 ISO Abbreviation: Scand. J. Immunol. Publication Date: 1998 Jul |
Date Detail:
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Created Date: 1998-09-23 Completed Date: 1998-09-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0323767 Medline TA: Scand J Immunol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 37-43 Citation Subset: IM |
Affiliation:
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Department of Nephrology, University Hospital Leiden, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Antineutrophil Cytoplasmic
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immunology* Apoptosis* Cells, Cultured Electrophoresis, Agar Gel Endothelium, Vascular / cytology*, immunology Humans Immunoglobulin G / immunology Neutrophils / immunology* Serine Endopeptidases / pharmacology, physiology* Wegener Granulomatosis / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Antineutrophil Cytoplasmic; 0/Immunoglobulin G; EC 3.4.21.-/Serine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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