caa a22 4500 378874357 CHVBK 20180305123417.0 cr unu---uuuuu 161128e20030220xx s 000 0 eng 10.1515/BC.2003.035 doi (NATIONALLICENCE)gruyter-10.1515/BC.2003.035 Protease Inhibitors Prevent Plasminogen-Mediated, But Not Pemphigus Vulgaris-Induced, Acantholysis in Human Epidermis [Elektronische Daten] [T. Schuh, R. Besch, E. Braungart, M.J. Flaig, K. Douwes, C.A. Sander, V. Magdolen, C. Probst, K. Wosikowski, K. Degitz] 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 Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence Schuh T. aut Besch R. aut Braungart E. aut Flaig M.J. aut Douwes K. aut Sander C.A. aut Magdolen V. aut Probst C. aut Wosikowski K. aut Degitz K. aut Biological Chemistry Walter de Gruyter 384/2(2003-02-20), 311-315 1431-6730 384:2<311 2003 384 bchm https://doi.org/10.1515/BC.2003.035 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2003.035 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schuh T. aut NATIONALLICENCE 700 1- Besch R. aut NATIONALLICENCE 700 1- Braungart E. aut NATIONALLICENCE 700 1- Flaig M.J. aut NATIONALLICENCE 700 1- Douwes K. aut NATIONALLICENCE 700 1- Sander C.A. aut NATIONALLICENCE 700 1- Magdolen V. aut NATIONALLICENCE 700 1- Probst C. aut NATIONALLICENCE 700 1- Wosikowski K. aut NATIONALLICENCE 700 1- Degitz K. aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 384/2(2003-02-20), 311-315 1431-6730 384:2<311 2003 384 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter