CHARACTERIZATION OF BIOLOGICALLY-ACTIVE ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES INDUCED IN MICE - PATHOGENETIC ROLE IN EXPERIMENTAL VASCULITIS

Objective. To investigate the pathogenetic role of antineutrophil cyto plasmic antibodies (ANCA) in Wegener's granulomatosis (WG). Methods. B ALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANC A 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 vas culitis. Results. Mice immunized with human ANCA developed anti-human ANCA add anti-anti-human ANCA (mouse ANCA), while the controls did not develop these antibodies, Mouse ANCA were capable of inducing adhesio n of neutrophils to fibronectin and activating the respiratory burst i n neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, sugg esting vasculitis. Conclusion. The results suggest a pathogenic role o f ANCA in WG, and may imply that activation of neutrophils is the init iating event in the development of vasculitis in WG.