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

44 Citations (Scopus)

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

Fingerprint

Myeloblastin
Cloning
Vasculitis
Organism Cloning
Antineutrophil Cytoplasmic Antibodies
Chymopapain
Immunization
Immunodominant Epitopes
Granulomatosis with Polyangiitis
Substrate Specificity
Autoantibodies
Rats
Epitopes
Rodentia
Neutrophils
Peptide Hydrolases
Complementary DNA
Monoclonal Antibodies

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Cloning and functional expression of the murine homologue of proteinase 3 : Implications for the design of murine models of vasculitis. / Jenne, Dieter E.; Fröhlich, Leopold; Hummel, Amber M.; Specks, Ulrich.

In: FEBS Letters, Vol. 408, No. 2, 19.05.1997, p. 187-190.

Research output: Contribution to journalArticle

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