Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis
| Autor: | E Csernok, WL Gross, Werner-Johannes Mayet, C Szymkowiak, K H Meyer zum Büschenfelde |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Myeloblastin
Molecular Sequence Data Immunology Biology Autoantigens Biochemistry Antibodies Antineutrophil Cytoplasmic Antigen Western blot Proteinase 3 medicine Humans Autoantibodies Base Sequence medicine.diagnostic_test Serine Endopeptidases Granulomatosis with Polyangiitis Cell Biology Hematology Endothelial stem cell Monoclonal biology.protein Cytokines Tumor necrosis factor alpha Endothelium Vascular Antibody |
| Zdroj: | Blood. 82:1221-1229 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v82.4.1221.bloodjournal8241221 |
| Popis: | Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (PR-3), have proved to be a useful clinical tool confirming the diagnosis or monitoring disease activity of Wegener's granulomatosis (WG). Although several concepts concerning the pathophysiologic potentials of ANCA have been discussed, only sparse data about ANCA-endothelium interactions have been available. In this study, we have investigated the expression of PR-3 in cytokine- treated human endothelial cells using purified anti-PR-3 antibodies of patients with WG, murine and human monoclonal anti-PR-3 antibodies as probes. We were able to show that tumor necrosis factor-alpha, interleukin-1 alpha/beta, and interferon-gamma led to an increased PR-3 expression in the cytoplasm of endothelial cells by performing polymerase chain reaction analysis, Western blot, cyto-enzyme-linked immunosorbent assays, and confocal laser scanning microscopy. Moreover, PR-3 was also translocated into the cell membrane, becoming accessible to ANCA. Our data suggest a possible direct pathogenic effect of anti- PR-3 antibodies in WG and other vasculitides. Anti-PR-3 antibodies represent an important missing link in ANCA-endothelial interactions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|