Cloning and functional expression of the murine homologue of proteinase 3: Implications for the design of murine models of vasculitis

Dieter E. Jenne, Leopold Fröhlich, Amber M. Hummel, Ulrich Specks

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Anti-neutrophil cytoplasmic autoantibodies recognizing conformational epitopes (c-ANCA) of proteinase 3 (PR3) from azurophil granules are a diagnostic hallmark in Wegener's granulomatosis (WG). Because a functional PR3 homologue has not been identified in rodents, it is difficult to assess immunopathological responses in rats or mice immunized with patients' derived c-ANCA or human PR3. Here we report the full length cDNA cloning and functional expression of murine PR3 in HMC-1 cells, Recombinant murine PR3 shows highly similar substrate specificities towards synthetic peptides and is inhibited by human α1-proteinase inhibitor like human PR3. However, neither human c-ANCA, rabbit sera nor mouse monoclonal antibodies to human PR3 recognize the murine homologue. Consequently, it is unlikely that disease observed in mice after immunization with c-ANCA or human PR3 is caused by pathogenic antibodies directed against mouse PR3. Recombinant human-mouse chimaeric variants will be a valuable new tool to localize the discase-specific immunodominant epitopes in human PR3.

Original languageEnglish (US)
Pages (from-to)187-190
Number of pages4
JournalFEBS Letters
Volume408
Issue number2
DOIs
StatePublished - May 19 1997

Keywords

  • Anti-neutrophil cytoplasmic antibody
  • In vivo animal model
  • Neutrophil
  • Proteinase 3

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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