Search results for "Proteinase 3"

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…

Propeptide glycosylation and galectin‐3 binding decrease proteolytic activation of human proMMP‐9/progelatinase B

2019

Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation. The MMP‐9 propeptide is unique in the MMP family because of its post‐translational modification with an N‐linked oligosaccharide. ProMMP‐9 activation by MMP‐3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro‐AT) and carboxyterminal (pro‐CT) peptide. We chemically synthesized aglycosyl pro‐AT and pro‐CT and purified recombinant glycosylated pro‐ATS f−9. First, we report new cleavage sites in the MMP‐9 propeptide by MMP‐3 and neutrophil elastase. Additionally, we demonstrated with the use of western blot analysis a…

Antibodies to Cathepsin G in Crohn's disease

1992

. Antibodies directed against antigens in human neutrophils have proved to be of great diagnostic value in certain systemic vasculitides. Recent reports have focused the attention on these antigens as targets of antibodies in sera of patients with inflammatory bowel disease. We investigated the sera drawn from 60 patients suffering from biopsy proven Crohn's disease and 15 patients with active ulcerative colitis. Using sensitive enzyme-linked immunosorbent assays with purified antigens and Western blotting the following antibodies could be demonstrated: cathepsin G (cat-G) antibodies IgG 38.3%, IgM 13.3%, IgA 23.3% and antibodies against human leucocyte elastase (HLE) IgG, IgA, IgM 3.3%. Lo…

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…

Molecular interactions between human cartilaginous endplates and nucleus pulposus cells: a preliminary investigation.

2014

Study Design. Conditioned media (CM) of cartilaginous endplates (CEPs) of intervertebral discs were analyzed in a bioassay with regard to their influence on matrix turnover and inflammatory factors on nucleus pulposus (NP) cells of the same patient. CEP tissue underwent further histological and ultrastructural analysis. Objective. To identify possible interactions between the CEP and the disc via molecular factors that may influence disc matrix degradation and to determine degenerative changes of CEP tissue. Summary of Background Data. Impaired endplate perme-ability due to degeneration and calcification is considered to be a key contributor to disc degeneration. An upregulation of metallop…

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 …

Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants.

1995

Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle α-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase–3), and collagenase I (matrix metalloproteinase–1) mR…

Genetic abrogation of the fibronectin-α5β1 integrin interaction in articular cartilage aggravates osteoarthritis in mice.

2018

The balance between synthesis and degradation of the cartilage extracellular matrix is severely altered in osteoarthritis, where degradation predominates. One reason for this imbalance is believed to be due to the ligation of the α5β1 integrin, the classic fibronectin (FN) receptor, with soluble FN fragments instead of insoluble FN fibrils, which induces matrix metalloproteinase (MMP) expression. Our objective was to determine whether the lack of α5β1-FN binding influences cartilage morphogenesis in vivo and whether non-ligated α5β1 protects or aggravates the course of osteoarthritis in mice. We engineered mice (Col2a-Cre;Fn1RGE/fl), whose chondrocytes express an α5β1 binding-deficient FN, …

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…