Studies on functions of neutrophils in MPO-ANCA related glomerulonephiritis and plasma effect on MPO release from neutrophils

Abstract

In order to examine the role of myeloperoxidase (MPO) and neutrophil activation in the pathogenesis of MPO-ANCA related necrotizing crescentic glomerulonephritis (GN), we investigated MPO release and superoxide anion (O-2) production from the neutrophils in MPO ANCA related GN. Plasma effect on MPO release from neutrophils was also studied in MPO-ANCA related GN. Neutrophils and plasma were obtained from 10 patients with MPO-ANCA-related GN (A), 10 patients with MPO-ANCA non related GN (B) and 10 healthy controls (C). MPO release and O-2 production were assayed by using chemotactic factor, N-formyl-methionyl-leucyl-phenyalanine (FMLP) and cytochalasin B (CB). In MPO-ANCA related GN, MPO release and O-2 production were significantly higher than in the other groups. [MPO release (%) A: 43.02 +/- 18.33, B: 33.26 +/- 11.58, C: 19.73 +/- 8.38, sensitivity to FMLP (%) A: 894.56 +/- 381.96, B: 512.86 +/- 314.91, C: 301.12 +/- 139.8, O-2 production (nmoles/min/10(6) cells) A: 13.06 +/- 5.28, B: 3.57 +/- 2.02, C: 2.83 +/- 1.16] Furthermore, MPO release, sensitivity to FMLP and O-2 production were shown to increase in parallel with clinical disease activity. Plasma from MPO-ANCA related GN increased sensitivity to FMLP in neutrophils obtained from healthy controls [plasma concentration 1%, A: 311.5 +/- 110.3, B: 227.2 +/- 101.4, C: 215.5 +/- 93.7], and plasma from MPO-ANCA related GN suppressed %MPO release from neutrophils with MPO-ANCA related GN [plasma concentration 0.1%, A: 11.56 +/- 6.17, C: 15.51 +/- 8.01]. It was concluded that in patients with MPO-ANCA related GN, large amounts of MPO can be easily released from activated neutrophils and this might be influenced by some stimulating and suppressing factors contained in the plasma.