Activities of superoxide dismutases and NADPH oxidase in neutrophils obtained from asthmatic and normal donors.
Activities of superoxide dismutases and NADPH oxidase in neutrophils obtained from asthmatic and normal donors.
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从哮喘和正常供体获得的中性粒细胞中超氧化物歧化酶和 NADPH 氧化酶的活性。
DOI：
10.1007/bf00918997
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发表时间：
1993
期刊：
影响因子：
5.1
通讯作者：
Borish,L
中科院分区：
文献类型：
--
作者：
Joseph,BZ;Routes,JM;Borish,L
与正常人相比，哮喘受试者的PMN表现出呼吸爆发增加，超氧化物生成增加。这种增强的超氧阴离子生成可能是继发于呼吸爆发NADPH氧化酶活性增加或通过超氧化物歧化酶（SOD）减少超氧化物的代谢。研究了哮喘患者PMN中表达的两种形式的SOD，即胞液中组成型表达的CuZnSOD和诱导型线粒体MnSOD。休息？与对照组相比，哮喘患者（N =9）的MN含有显著较低的MnSOD活性（分别为0.46 ± 0.16和0.79 ± 0.17单位/107 PMN;P=0.0002）。由于白细胞介素（IL）-1、-4、-6、粒细胞巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子（TNF）等细胞因子能促进PMN呼吸爆发，并在哮喘肺内合成，因此，本实验测定了它们对PMN MnSOD活性的影响。与其对淋巴细胞的作用相反，IL-1和IL-6以剂量依赖的方式显著抑制正常人PMN中MnSOD的诱导（在每种细胞因子10单位/ml时，分别为0.42 ± 0.12和0.45 ± 0.05单位/107 PMN;与静息细胞相比，P=0.02），但未能进一步调节哮喘PMN中MnSOD的产生。IL-4和GM-CSF对MnSOD的产生没有影响，由于TNF对细胞活力的影响，因此无法研究TNF的影响。CuZnSOD（N=9）和NADPH氧化酶（N =4）的活性在两组间无差异。抑制MnSOD活性的PMN继发于细胞因子暴露在哮喘肺可以解释，至少部分地，从哮喘患者获得的PMN产生的超氧化物的增加。这将促进哮喘肺部炎症的存在和严重程度。这些数据进一步支持IL-1和IL-6在过敏性炎症中的作用。
PMN obtained from asthmatic subjects demonstrate a heightened respiratory burst with increased superoxide generation compared to normals. This enhanced superoxide anion generation could be secondary to increased activity of the respiratory burst NADPH oxidase or diminished metabolism of superoxide via superoxide dismutase (SOD). The two forms of SOD expressed in PMN, CuZnSOD expressed constitutively in the cytosol and inducible mitochondrial MnSOD, were investigated in asthmatics. Resting ?MN from asthmatics (N =9) contained significantly less MnSOD activity compared to controls (0.46 ± 0.16 vs. 0.79 ± 0.17 units/107PMN, respectively;P=0.0002). As several cytokines including interleukins (IL) -1, -4, and -6 as well as granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) enhance the PMN respiratory burst and are synthesized in the asthmatic lung, their effects on PMN MnSOD activity were assayed. In contrast to its effects on lymphocytes, both IL-1 and IL-6 significantly inhibited in a dosedependent fashion the induction of MnSOD in PMN from normals (0.42 ± 0.12 and 0.45 ± 0.05 units/107PMN, respectively, at 10 units/ml of each cytokine;P=0.02 compared to resting cells) but failed to further modulate MnSOD production in asthmatic PMN. IL-4 and GM-CSF had no effect on MnSOD production, and TNF effects could not be studied because of its effects on cell viability. There were no differences in the activity of CuZnSOD (N=9) or NADPH oxidase (N =4) in the two groups. Inhibition of MnSOD activity in PMN secondary to cytokine exposure in the asthmatic lung could explain, at least in part, the increased generation of superoxide from PMN obtained from asthmatics. This would promote the presence and severity of inflammation in the asthmatic lung. These data further support a role for IL-1 and IL-6 in allergic inflammation.