Minoshima S
First Department of Internal Medicine, Kyorin University, School of Medicine, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1995 Sep;37(9):481-90.
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.
为了研究髓过氧化物酶(MPO)和中性粒细胞活化在MPO-ANCA相关性坏死性新月体性肾小球肾炎(GN)发病机制中的作用,我们调查了MPO-ANCA相关性GN患者中性粒细胞中MPO的释放及超氧阴离子(O₂)的产生情况。同时还研究了血浆对MPO-ANCA相关性GN患者中性粒细胞释放MPO的影响。从10例MPO-ANCA相关性GN患者(A组)、10例MPO-ANCA非相关性GN患者(B组)和10名健康对照者(C组)获取中性粒细胞和血浆。使用趋化因子N-甲酰甲硫氨酰亮氨酰苯丙氨酸(FMLP)和细胞松弛素B(CB)检测MPO释放及O₂产生情况。在MPO-ANCA相关性GN患者中,MPO释放及O₂产生显著高于其他组。[MPO释放率(%):A组43.02±18.33,B组33.26±11.58,C组19.73±8.38;对FMLP的敏感性(%):A组894.56±381.96,B组512.86±314.91,C组301.12±139.8;O₂产生量(nmol/min/10⁶细胞):A组13.06±5.28,B组3.57±2.02,C组2.83±1.16]此外,MPO释放、对FMLP的敏感性及O₂产生量与临床疾病活动度呈平行增加。MPO-ANCA相关性GN患者的血浆增加了健康对照者中性粒细胞对FMLP的敏感性[血浆浓度1%时:A组311.5±110.3,B组227.2±101.4,C组215.5±93.7],且MPO-ANCA相关性GN患者的血浆抑制了MPO-ANCA相关性GN患者中性粒细胞的MPO释放率[血浆浓度0.1%时:A组11.56±6.17,C组15.51±8.01]。得出的结论是,在MPO-ANCA相关性GN患者中,大量MPO可轻易从活化的中性粒细胞中释放出来,这可能受血浆中某些刺激和抑制因子的影响。