title: Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice. Pathogenetic role in experimental vasculitis.
abstract: OBJECTIVE
  To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG).
  
  
  METHODS
  BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis.
  
  
  RESULTS
  Mice immunized with human ANCA developed anti-human ANCA and anti-anti-human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis.
  
  
  CONCLUSIONS
  The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.
authors.affiliation: Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Tomer
authors.forename: B
authors.initials: B
authors.lastname: Gilburd
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: O
authors.initials: O
authors.lastname: Lider
authors.forename: R
authors.initials: R
authors.lastname: Hershkoviz
authors.forename: P
authors.initials: P
authors.lastname: Fishman
authors.forename: R
authors.initials: R
authors.lastname: Zigelman
authors.forename: P L
authors.initials: PL
authors.lastname: Meroni
authors.forename: A
authors.initials: A
authors.lastname: Wiik
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D005260:Female; D005353:Fibronectins; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D016897:Respiratory Burst
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D005353:Fibronectins