Methylprednisolone normalizes superoxide anion production by polymorphs from patients with ANCA-positive vasculitides.

Methylprednisolone normalizes superoxide anion production by polymorphs from patients with ANCA-positive vasculitides.
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甲基泼尼松龙可使 ANCA 阳性血管炎患者的多晶型物产生的超氧阴离子正常化。

DOI:
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发表时间:
1993
影响因子:
19.6
通讯作者:
G. Remuzzi
G. Remuzzi
中科院分区:
医学1区
文献类型:
--
作者:
D. Macconi;A. F. Zanoli;S. Orisio;L. Longaretti;L. Magrini;S. Rota;A. Radice;C. Pozzi;G. Remuzzi

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在实验性肾小球肾炎中,中性粒细胞活化释放的活性氧介导了肾小球损伤。最近的研究发现,抗中性粒细胞胞质自身抗体(ANCA)诱导中性粒细胞去角质,并产生氧自由基在体外导致我们探讨是否中性粒细胞ANCA阳性血管炎和坏死性肾小球肾炎患者产生的超氧阴离子(O2-)的量增加。由于糖皮质激素在体外抑制氧自由基的产生,我们还评估了甲基强的松龙静脉冲击的效果。从外周血中分离出多态性,收集前(基础),6和24小时后,第一次输注甲泼尼龙和24小时后,第三个。在没有特定刺激的情况下孵育30分钟后评估细胞的O2释放。基础O2-释放在患者组显著高于对照组(P < 0.01)。静脉输注高剂量的甲基强的松龙显着降低O2-生产相对于基础值,差异有统计学意义,在各种时间间隔后考虑类固醇输注。除了减少过量的O2-形成,甲基强的松龙诱导锰超氧化物歧化酶(Mn-SOD)酶的基因编码的多晶型表达的增加。我们的结论是,从ANCA阳性血管炎和坏死性肾小球肾炎患者中提取的多晶型物产生的O2-比正常人高。甲基强的松龙使O2-的异常产生正常化,可能是通过其上调Mn-SOD基因的能力,Mn-SOD是一种有效的抗氧化酶。
It has been convincingly documented that reactive oxygen species released from activated neutrophils mediate glomerular damage in experimental glomerulonephritis. Recent findings that antineutrophil cytoplasmic autoantibodies (ANCA) induce neutrophils to degranulate and produce oxygen radicals in vitro led us to explore whether neutrophils from patients with ANCA-positive vasculitides and necrotizing glomerulonephritis generated an increased amount of superoxide anion (O2-). Since glucocorticoids inhibit oxygen radicals generation in vitro we also evaluated the effect of intravenous pulses of methylprednisolone. Polymorphs were isolated from peripheral blood collected before (basal), 6 and 24 hours after the first infusion of methylprednisolone and 24 hours after the third one. O2- release by cells was assessed after 30 minute incubation without specific stimuli. Basal O2- release was significantly higher in patients than in controls (P < 0.01). Intravenous infusion of high doses of methylprednisolone markedly reduced O2- production with respect to the basal value, and the difference was statistically significant at various time interval considered after the steroid infusion. Besides reducing the excessive O2- formation, methylprednisolone induced an increase in polymorph expression of the gene encoding for manganese superoxide dismutase (Mn-SOD) enzyme. We conclude that polymorphs taken from patients with ANCA-positive vasculitides and necrotizing glomerulonephritis generate higher amounts of O2- than those from normal subjects. Methylprednisolone normalizes the abnormal generation of O2-, likely through its ability to up-regulate the gene for Mn-SOD, a potent antioxidant enzyme.
DOI: 10.1182/blood.v69.5.1409.1409
发表时间: 1987-05
期刊: Blood
影响因子: 20.3
作者:
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通讯作者: A. Rambaldi;D. Young;James D. Griffin
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DOI: 10.1152/ajprenal.1989.257.1.f53
发表时间: 1989
期刊: The American journal of physiology
影响因子: --
作者:
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DOI: 10.1172/jci112965
发表时间: 1987-05-01
影响因子: 15.9
作者:
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通讯作者: KLEBANOFF, SJ
DOI: --
发表时间: 1984
期刊: Laboratory investigation; a journal of technical methods and pathology
影响因子: --
作者:
Cavallo,T;Graves,K;Granholm,NA
通讯作者: Granholm,NA
DOI: 10.1073/pnas.87.4.1620
发表时间: 1990-02-01
影响因子: 11.1
作者:
BECKMAN, JS;BECKMAN, TW;FREEMAN, BA
通讯作者: FREEMAN, BA