No activation of urokinase plasminogen activator by anti-desmoglein 3 monoclonal IgG antibodies in cultured human keratinocytes

Yukari Yamamoto, Yumi Aoyama, En Shu, Kazuyuki Tsunoda, Masayuki Amagai, Yasuo Kitajima

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Although pemphigus vulgaris (PV)-IgG has been shown to activate urokinase plasminogen activator (uPA) in cultured keratinocytes, activation of uPA is thought to have no primary role in PV-acantholysis, because PV-IgG is still pathogenic in uPA- and tissue-PA-knockout mice. Objective: To determine if PV-IgG-induced uPA activation is due to specific antibody against Dsg3, we examined whether or not pathogenic monoclonal anti-Dsg3 antibody can activate uPA, because PV-IgG is thought to contain antibodies against unknown antigens besides Dsg3. Methods: We stimulated cultured normal human and DJM-1 keratinocytes with monoclonal anti-Dsg3 IgG1 antibodies (pathogenic AK23, AK19 and nonpathogenic AK18, AK20), negative control monoclonal mouse IgG1 and positive control PV-IgG. Cells were treated with IgGs over a time course of 24 h, and uPA-protein content and activity in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA) and chromogenic assay, respectively. Results: The uPA-protein content in samples treated with or without pathogenic, nonpathogenic, control monoclonal mouse IgG1s and PV-IgGs increased continuously up to 24 h, with no differences between samples, suggesting a spontaneous secretion. In contrast, uPA activity in the culture medium of cells treated with PV-IgG increased dramatically, whereas that of cells treated with all AK-IgGs and control monoclonal mouse IgG1 did not increase at all. Conclusion: These results suggest that PV-IgG-dependent uPA activation is not related to anti-Dsg3 antibody activity, which is an essential factor in PV-IgG acantholysis, and that it may be due to other antigens than Dsg3 or unknown factors contained in PV-IgG fraction.

Original languageEnglish
Pages (from-to)119-125
Number of pages7
JournalJournal of Dermatological Science
Volume47
Issue number2
DOIs
Publication statusPublished - 2007 Aug 1

Keywords

  • Autoimmunity
  • Bullous disease
  • Keratinocytes
  • Pemphigus
  • Plasminogen activator

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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