Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies

Abstract

SUMMARY: Anti-neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminolamplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti-double stranded DNA positive sera (P<0·01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminesccnce system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f-Met-Leu-Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan-activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis.