The role of oxidative processes in emphysema.
The role of oxidative processes in emphysema.
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氧化过程在肺气肿中的作用。
DOI：
10.1164/arrd.1983.127.2p2.s31
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Raju,L
中科院分区：
文献类型：
--
作者：
Janoff,A;Carp,H;Laurent,P;Raju,L
肺中弹性蛋白酶/弹性蛋白酶抑制剂失衡与肺气肿的发病机制有关。鉴于此，氧化剂可降低两种主要弹性蛋白酶抑制剂α 1-蛋白酶抑制剂（α 1-抗胰蛋白酶，α 1 Pi）和支气管粘膜蛋白酶抑制剂的活性可能具有重要意义。这种效应可以在臭氧、香烟烟雾中存在的物质、肺巨噬细胞产生的氧代谢物以及其他吞噬细胞释放的过氧化系统中观察到。因此，从吸烟者肺洗涤液中回收的α 1 Pi每毫克抑制剂仅具有预测正常活性的一半，并且每摩尔非活性抑制剂含有4摩尔甲硫氨酸亚砜（氧化甲硫氨酸）。相比之下，从非吸烟者的肺冲洗液中纯化的α 1 Pi是完全活性的，仅含有天然的蛋氨酸。与此同时，一些吸烟者的肺洗涤液对特定合成弹性蛋白酶底物的水解活性明显高于非吸烟者的肺洗涤液。这些发现表明，一些吸烟者可能会在肺部的弹性蛋白酶和弹性蛋白酶抑制剂之间形成后天性的不平衡，从而有利于酶的活性。除了吸烟对肺弹性蛋白酶/弹性蛋白酶抑制剂平衡的潜在影响外，吸烟还可能干扰弹性蛋白修复机制。具体而言，香烟烟雾的酸性水溶性气相组分在体外弹性蛋白生成期间阻止锁链素交联的合成。本报告将试图将吸烟引起的肺部生化变化的上述信息与吸烟者肺气肿的发生联系起来。
Elastase/elastase inhibitor imbalance in the lung has been implicated in the pathogenesis of pulmonary emphysema. In light of this, it may be significant that the activity of two major elastase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin, α1Pi) and bronchial mucous proteinase inhibitor, can be decreased by oxidizing agents. The effect can be observed with ozone, substances present in cigarette smoke, and oxygen metabolites generated by lung macrophages as well as peroxidative systems released by other phagocytic cells. Thus α1Pi recovered from lung washings of cigarette smokers has only half the predicted normal activity per mg inhibitor and contains 4 moles of methionine sulfoxide (oxidized methionine) per mole of inactive inhibitor. By contrast, α1Pi purified from nonsmokers' lung washings is fully active and contains only native methionine. At the same time, lung washes from some smokers show significantly greater hydrolytic activity against a specific synthetic elastase substrate than do lung washes of nonsmokers. These findings suggest that some smokers may develop an acquired imbalance between elastase and elastase inhibitor in their lungs, favoring activity of the enzyme. In addition to the potential effect of cigarette smoking on lung elastase/elastase inhibitor balance, smoking also may interfere with elastin repair mechanisms. Specifically, acidic water-soluble gas phase components of cigarette smoke prevent synthesis of desmosine cross-links during elastinogenesisin vitro. This report will attempt to correlate the foregoing information on biochemical changes in the lung induced by cigarette smoking with the development of emphysema in the smoker.