Protease Inhibitors Prevent Plasminogen-Mediated, But Not Pemphigus Vulgaris-Induced, Acantholysis in Human Epidermis
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T. Schuh
Abstract
Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. It is caused by autoantibodies directed against desmosomes, which are the principal adhesion structures between epidermal keratinocytes. Binding of autoantibodies leads to the destruction of desmosomes resulting in the loss of cell-cell adhesion (acantholysis) and epidermal blisters. The plasminogen activator system has been implicated as a proteolytic effector in pemphigus. We have tested inhibitors of the plasminogen activator system with regard to their potential to prevent pemphigusinduced cutaneous pathology. In a human split skin culture system, IgG preparations of sera from pemphigus vulgaris patients caused histopathologic changes (acantholysis) similar to those observed in the original pemphigus disease. All inhibitors that were tested (active site inhibitors directed against uPA, tPA, and/or plasmin; antibodies neutralizing the enzymatic activity of uPA or tPA; substances interfering with the binding of uPA to its specific cell surface receptor uPAR) failed to prevent pemphigus vulgaris IgG-mediated acantholysis. Plasminogen mediated acantholysis, however, was effectively antagonized by the synthetic active site serine protease inhibitor WX-UK1 or by p-aminomethylbenzoic acid. Our data argue against applying anti-plasminogen activator/anti-plasmin strategies in the management of pemphigus.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Obituary
- Thrombin Signaling in the Brain: The Role of Protease-Activated Receptors
- Transcriptional Repression of the Human p53 Gene by Hepatitis B Viral Core Protein (HBc) in Human Liver Cells
- Identification of Cytosolic Leucyl Aminopeptidase (EC 3.4.11.1) as the Major Cysteinylglycine-Hydrolysing Activity in Rat Liver
- A Novel Influenza A Virus Activating Enzyme from Porcine Lung: Purification and Characterization
- Binding of Urokinase Plasminogen Activator to gp130 via a Putative Urokinase-Binding Consensus Sequence
- Modifications of Glyceraldehyde-3-Phosphate Dehydrogenase Induced by Increasing Concentrations of Peroxynitrite: Early Recognition by 20S Proteasome
- Different Isoforms of the Non-Integrin Laminin Receptor Are Present in Mouse Brain and Bind PrP
- Cell-Type Specific Targeting and Gene Expression Using a Variant of Polyoma VP1 Virus-Like Particles
- Quantitation of Membrane Type Serine Protease 1 (MT-SP1) in Transformed and Normal Cells
- Interaction of Heat Shock Protein 70 Peptide with NK Cells Involves the NK Receptor CD94
- Cystatins C, E/M and F in Human Pleural Fluids of Patients with Neoplastic and Inflammatory Lung Disorders
- A Homodimeric Sporamin-Type Trypsin Inhibitor with Antiproliferative, HIV Reverse Transcriptase-Inhibitory and Antifungal Activities from Wampee (Clausena lansium) Seeds
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- Diverse Enzymatic Specificities of Digestive Proteases, 'Intestains', Enable Colorado Potato Beetle Larvae to Counteract the Potato Defence Mechanism
- Protease Inhibitors Prevent Plasminogen-Mediated, But Not Pemphigus Vulgaris-Induced, Acantholysis in Human Epidermis
- Purification and Primary Structure Determination of Human Lysosomal Dipeptidase
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