Increased release of myeloperoxidase in vitro from neutrophils of patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis

Summary: In order to elucidate the role of neutrophils in the pathogenesis of MPO-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis (GN), MPO release, beta-glucuronidase (BGL) release, superoxide anion (O₂⁻) production from the neutrophils of patients with MPO-ANCA related GN were measured. the effect of plasma on MPO release from neutrophils was also studied in patients with MPO-ANCA related GN. Neutrophils and plasma were obtained from patients with MPO-ANCA related GN, GN unrelated to MPO-ANCA and healthy controls. MPO release from the neutrophils of patients with MPO-ANCA related GN was higher than that of controls significantly. This was also higher than that in patients with GN unrelated to MPG-ANCA, but this was not statistically significant. Superoxide anion production from neutrophils of patients with MPO-ANCA related GN was significantly higher than that in patients with GN unrelated MPO-ANCA, However, BGL release was not significantly different among three groups. Furthermore, MPO release and O₂⁻ production increased in parallel with clinical activity of MPO-ANCA related GN. Neutrophils of patients with MPO-ANCA related GN showed to be significantly more sensitive to FMLP on MPO release than those in the other two groups. However, plasma from MPO-ANCA related GN increased the sensitivity to FMLP on MPO release, but not BGL release, in neutrophils obtained from healthy controls, whereas it suppressed MPO release from neutrophils with MPO-ANCA related GN. This suggests that in patients with MPO-ANCA related GN MPO can be highly released from activated neutrophils and that the plasma of patients with MPO-ANCA contains factor(s) which modulate reactivity of neutrophils.