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在人类吞噬细胞的N-甲酰肽激活过程中,抗坏血酸盐和半胱氨酸介导的细胞外氧化剂选择性中和作用

Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes.

作者信息

Anderson R, Lukey P T, Theron A J, Dippenaar U

出版信息

Agents Actions. 1987 Feb;20(1-2):77-86. doi: 10.1007/BF01965628.

DOI:10.1007/BF01965628
PMID:3034003
Abstract

The effects of sodium ascorbate and cysteine (2.5 X 10(-5) M-2.5 X 10(-4) M) on the intensity and profile of luminol-enhanced chemiluminescence, superoxide generation, extracellular myeloperoxidase (MPO) activity and auto-iodination were measured in purified human polymorphonuclear leukocytes activated by the leukoattractant FMLP in vitro. Chemiluminescence studies were also performed using a whole-blood method. Cysteine (10(-4) M-2.5 X 10(-4) M) and ascorbate (2.5 X 10(-5) M-2.5 X 10(-4) M) caused significant inhibition of the early extracellular peak of FMLP-activated chemiluminescence and increased the intensity of the later occurring intracellular peak in both PMNL and blood. At the same concentrations both agents scavenged superoxide released by FMLP-activated PMNL, inhibited oxidant generation by extracellular MPO and decreased FMLP-induced auto-oxidation of PMNL. Administration of a single 1 gram oral dose of ascorbate to adult human volunteers was associated with significant reduction and enhancement respectively of the extracellular and intracellular luminol-enhanced chemiluminescence responses of FMLP-activated blood. These results show that the water soluble anti-oxidants cysteine and especially ascorbate selectively neutralise the reactivity of harmful reactive oxidants released by phagocytes, whilst the intracellular generation of antimicrobial oxidants remains intact.

摘要

在体外,通过白细胞趋化因子FMLP激活纯化的人多形核白细胞,测定了抗坏血酸钠和半胱氨酸(2.5×10⁻⁵M - 2.5×10⁻⁴M)对鲁米诺增强的化学发光强度和曲线、超氧化物生成、细胞外髓过氧化物酶(MPO)活性及自身碘化的影响。还采用全血法进行了化学发光研究。半胱氨酸(10⁻⁴M - 2.5×10⁻⁴M)和抗坏血酸盐(2.5×10⁻⁵M - 2.5×10⁻⁴M)显著抑制了FMLP激活的化学发光的早期细胞外峰,并增加了在多形核白细胞和血液中随后出现的细胞内峰的强度。在相同浓度下,两种试剂都清除了FMLP激活的多形核白细胞释放的超氧化物,抑制了细胞外MPO产生的氧化剂,并减少了FMLP诱导的多形核白细胞的自氧化。给成年人类志愿者口服单次1克剂量的抗坏血酸盐,分别与FMLP激活的血液的细胞外和细胞内鲁米诺增强的化学发光反应的显著降低和增强有关。这些结果表明,水溶性抗氧化剂半胱氨酸,尤其是抗坏血酸盐,选择性地中和了吞噬细胞释放的有害活性氧化剂的反应性,而细胞内抗菌氧化剂的产生保持完整。

相似文献

1
Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes.在人类吞噬细胞的N-甲酰肽激活过程中,抗坏血酸盐和半胱氨酸介导的细胞外氧化剂选择性中和作用
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2
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3
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Lung. 1988;166(3):149-59. doi: 10.1007/BF02714043.
4
Investigation of the protective effects of the antioxidants ascorbate, cysteine, and dapsone on the phagocyte-mediated oxidative inactivation of human alpha-1-protease inhibitor in vitro.体外研究抗氧化剂抗坏血酸盐、半胱氨酸和氨苯砜对吞噬细胞介导的人α-1-蛋白酶抑制剂氧化失活的保护作用。
Am Rev Respir Dis. 1985 Nov;132(5):1049-54. doi: 10.1164/arrd.1985.132.5.1049.
5
Benoxaprofen: a pro-oxidant anti-inflammatory drug?苯恶洛芬:一种促氧化抗炎药物?
Agents Actions. 1984 Feb;14(2):238-46. doi: 10.1007/BF01966648.
6
Clofazimine-mediated regulation of human polymorphonuclear leukocyte migration by pro-oxidative inactivation of both leukoattractants and cellular migratory responsiveness.氯法齐明通过对白细胞趋化因子和细胞迁移反应性进行促氧化失活,介导对人多形核白细胞迁移的调控。
Int J Immunopharmacol. 1986;8(6):605-20. doi: 10.1016/0192-0561(86)90033-0.
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Luminol-enhanced chemiluminescence induced in peripheral blood-derived human phagocytes: obligatory requirement of myeloperoxidase exocytosis by monocytes.外周血来源的人类吞噬细胞中鲁米诺增强的化学发光:单核细胞髓过氧化物酶胞吐作用的必要条件。
J Leukoc Biol. 1993 Oct;54(4):300-6. doi: 10.1002/jlb.54.4.300.
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Inhibitory effect of stobadine on FMLP-induced chemiluminescence in human whole blood and isolated polymorphonuclear leukocytes.司托巴定对人全血和分离的多形核白细胞中FMLP诱导的化学发光的抑制作用。
Luminescence. 2007 Mar-Apr;22(2):67-71. doi: 10.1002/bio.919.
9
Oxidative inhibition of polymorphonuclear leukocyte motility mediated by the peroxidase/H2O2/halide system: studies on the reversible nature of the inhibition and mechanism of protection of migratory responsiveness by ascorbate, levamisole, thiamine and cysteine.过氧化物酶/H2O2/卤化物系统介导的多形核白细胞运动的氧化抑制作用:关于抑制作用的可逆性以及抗坏血酸、左旋咪唑、硫胺素和半胱氨酸对迁移反应性保护机制的研究。
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Investigation of the effects of oral administration of ascorbate on the functional activity of serum alpha-1-protease inhibitor and oxidant release by blood phagocytes from cigarette smokers in a placebo-controlled, doubleblind, crossover trial.在一项安慰剂对照、双盲、交叉试验中,研究口服抗坏血酸盐对吸烟者血清α-1-蛋白酶抑制剂功能活性及血液吞噬细胞氧化剂释放的影响。
Int J Vitam Nutr Res. 1988;58(2):218-24.

本文引用的文献

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Spectrum of horse-heart cytochrome c.马心细胞色素c的光谱
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Increased leucoattractant binding and reversible inhibition of neutrophil motility mediated by the peroxidase/H2O2/halide system: effects of ascorbate, cysteine, dithiothreitol, levamisole and thiamine.过氧化物酶/H2O2/卤化物系统介导的白细胞趋化因子结合增加及中性粒细胞运动的可逆抑制:抗坏血酸、半胱氨酸、二硫苏糖醇、左旋咪唑和硫胺素的作用。
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Effects of oxygen radical scavengers and antioxidants on phagocyte-induced mutagenesis.氧自由基清除剂和抗氧化剂对吞噬细胞诱导的诱变作用。
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Modification of cellular protein sulfhydryl groups by activated soluble immune response suppressor.活化的可溶性免疫反应抑制因子对细胞蛋白巯基的修饰作用。
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9
Suppression of human lymphocyte mitogenesis mediated by phagocyte-released reactive oxygen species: comparative activities in normals and in chronic granulomatous disease.吞噬细胞释放的活性氧介导的人淋巴细胞有丝分裂抑制:正常人和慢性肉芽肿病中的比较活性
Clin Immunol Immunopathol. 1984 Jul;32(1):29-40. doi: 10.1016/0090-1229(84)90040-0.
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The role of oxidative processes in emphysema.氧化过程在肺气肿中的作用。
Am Rev Respir Dis. 1983 Feb;127(2):S31-8. doi: 10.1164/arrd.1983.127.2P2.S31.