We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immuno...

INTRODUCTION Proteinase 3 (PR3) is released from neutrophil azurophilic granules and exerts complex effects on the inflammatory process. PR3 catalyzes the degradation of a number of macromolecules, but the consequences on blood cells are less well defined. In the present study, the effect of PR3 on human platelets was thoroughly investigated. METHODS The experiments were performed on washed p...

We herein report two cases of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA)-related nephritis in infectious endocarditis. In both cases, the patients were middle-aged men with proteinuria and hematuria, hypoalbuminemia, decreased kidney function, anemia, elevated C-reactive protein (CRP) levels, and PR3-ANCA positivity. Each had bacteremia, due to Enterococcus faecium in one and ...

Wegener's granulomatosis (WG) is an inflammatory disorder characterized by granulomatous inflammation and vasculitis, and is strongly associated with antineutrophil cytoplasmic antibodies (ANCA). ANCA in patients with WG are directed against proteinase 3 (Pr3) in most of the cases. In vitro, upon neutrophil priming, ANCA antigens are expressed on the cell surface, thereby becoming available for...

During systemic inflammation, neutrophil activation is accompanied by endothelial cell damage and hypercoagulability. Activated neutrophils release serine proteases that participate in tissue injury. We sought to investigate the effects of neutrophil proteases on proinflammatory and procoagulant changes in endothelial cells. The effects of elastase (HNE), cathepsin G (CG), and proteinase 3 (PR3...

Antineutrophil cytoplasmic autoantibody (ANCA) causes vascular injury that leads to small-vessel vasculitis. Patients with ANCA aberrantly express neutrophil granule-encoding genes, including 2 that encode autoantigens: proteinase 3 (PR3) and myeloperoxidase (MPO). To uncover a potential transcriptional regulatory mechanism for PR3 and MPO disrupted in patients with ANCA vasculitis, we examined...

IL-32, a recently discovered proinflammatory cytokine with four isoforms, induces IL-1beta, TNF-alpha, IL-6, and chemokines. Here, we used ligand (IL-32alpha) affinity chromatography in an attempt to isolate an IL-32alpha soluble receptor or binding protein. Recombinant IL-32alpha was covalently immobilized on agarose, and preparations of concentrated crude human urinary proteins were applied f...

Anti-neutrophil cytoplasmic Abs (cANCAs) against conformational epitopes of proteinase 3 (PR3) are regarded as an important pathogenic marker in Wegener's granulomatosis (WG). Although the three-dimensional structure of PR3 is known, binding sites of mAbs and cANCAs have not been mapped to date. Competitive binding and biosensor experiments suggested the existence of four nonoverlapping areas o...

BACKGROUND AND OBJECTIVES The subclinical pathogenesis of granulomatosis with polyangiitis (GPA) has not been completely elucidated. Proteinase 3 (PR3) antibodies are strongly associated with GPA, but have not been evaluated before disease presentation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a retrospective case-control serum bank study in which PR3 antibodies and C-reactive p...

Leukocyte-derived proteases have long been considered simply degradative. However, emerging data raise possibilities of a complex and specific biologic role for these proteases in substrate processing and in signaling pathways within cells. This study reports that the release of neutrophilic and monocytic proteases, such as proteinase 3 (PR3) and human neutrophil elastase (HNE), can result in t...