Search results for "Myeloblastin"

Genetics and pathophysiology of granulomatosis with polyangiitis (GPA) and its main autoantigen proteinase 3.

2016

Granulomatosis with polyangiitis (GPA) is a severe autoimmune disease and one of the small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although its etiology and pathophysiology are still widely unknown, it is accepted that infections, environmental factors, epigenetic modifications, and a genetic predisposition provide the basis for this systemic disorder. GPA typically evolves into two phases: an initial phase characterized by ear, nose and throat (ENT) manifestations, such as chronic sinusitis and otitis, ulceration of the oral cavity and pharynx, as well as pulmonary nodules and a severe generalized phase, defined by the occurrence of rapidly progressive g…

Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis

2000

Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis. Background Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG. Since the kidneys are frequently involved in WG, we studied the in situ expression of PR-3 by renal parenchymal cells. Methods We assessed the expression of PR-3 in kidney biopsies of 15 patien…

Human renal tubular epithelial cells as target cells for antibodies to proteinase 3 (c-ANCA)

1997

In Vitro Interactions of C-ANCA (Antibodies to Proteinase 3) with Human Endothelial Cells

1993

Several concepts concerning the pathogenicity of antineutrophil cytoplasmic antibodies (ANCA) exist, but till now only sparse data about ANCA-endothelial interactions are available. In this study we have investigated the expression of proteinase 3 (PR-3) in human umbilical endothelial cells (HEC) using purified anti-PR3 antibodies (C-ANCA) of patients with Wegener’s granulomatosis (WG) and monoclonal antibodies to PR-3 (human and murine) as probes. Performing cytoELISAs, laser scanning microscopy and Western blot we were able to show that treatment of HEC with IL-1-alpha led to an increased PR-3 expression in the cytoplasm and to a transient translocation into the EC-membrane. Representing …

Cytotoxic effects of antibodies to proteinase 3 (C-ANCA) on human endothelial cells.

1994

SUMMARY Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially those with specificity for proteinase 3 (PR-3) and myeloperoxidase, are valuable markers for differential diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG) and other vasculitides. Till now, several concepts concerning a direct role of antibodies against PR-3 in the pathogenesis of WG have been discussed. Recently we were able to show that these antibodies recognize PR-3 translocated into the membrane of human endothelial cells. The aim of this study was to investigate putative cytotoxic effects of antibodies to PR-3 on human endothelial cells. Antibodies were obtained b…

Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial cells

1993

SUMMARY The detection of anti-neutrophil cytoplasmic antibodies (ANCA), especially those with specificity for proteinase 3, is important in the diagnosis and in monitoring disease activity of Wegener's granulomatosis and related vasculitides. An ubiquitous feature of all ANCA-associated acute vascular injury is lytic necrosis. Adhesion of neutrophils to endothelium is a fundamental early step of the inflammatory response. Recently we were able to show that ANCA recognize their target antigen (proteinase 3) translocated into the membrane of human endothelial cells. The aim of this study was to investigate the effect of ANCA on the adhesion of neutrophils to human endothelial cells. Incubatio…

Interaction of antibodies to proteinase 3 (classic anti-neutrophil cytoplasmic antibody) with human renal tubular epithelial cells: impact on signali…

2002

Abstract Among the anti-neutrophil cytoplasmic Abs (ANCA), those targeting proteinase 3 (PR3) have a high sensitivity and specificity for Wegener’s granulomatosis (WG). A pathogenetic role for these autoantibodies has been proposed due to their capacity of activating neutrophils in vitro. Recently, PR3 was also detected in human renal tubular epithelial cells (TEC). In the present study, the effect of murine monoclonal anti-PR3 Abs (anti-PR3) and purified c-ANCA targeting PR3 from WG serum on isolated human renal tubular cell signaling and inflammatory mediator release was characterized. Priming of TEC with TNF-α resulted in surface expression of PR3, as quantified in immunofluorescence stu…

Vasculitic wallenberg syndrome with detection of anti-proteinase 3 antibodies in the cerebrospinal fluid of a patient with severe Wegener's granuloma…

2000

Signal transduction pathways of membrane expression of proteinase 3 (PR‐3) in human endothelial cells

1997

At present, the exact mechanism of the pathogenic effect of anti-PR-3 antibodies remains unknown. Interaction of anti-neutrophil cytoplasmic antibodies (ANCAs) with human umbilical vein endothelial cells (HUVECs) may play a key role. Recently we were able to show that ANCAs recognize their target antigen, PR-3, translocated into the membrane of HUVECs. The objective of this study was to investigate regulation, i.e. signal transduction pathways, of PR-3 expression in endothelial cells. HUVECs were isolated according to the method of Jaffe et al. and cultured under standard conditions. A cyto-enzyme-linked immunosorbent assay (ELISA) with unfixed cells was performed. Membrane-expressed PR-3 w…

Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis

1993

Abstract 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, int…