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

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 alpha 1-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 disease-specific immunodominant epitopes in human PR3. (C) 1997 Federation of European Biochemical Societies.