POTENTIAL MECHANISM OF EMPHYSEMA - ALPHA-1-PROTEINASE INHIBITOR RECOVERED FROM LUNGS OF CIGARETTE SMOKERS CONTAINS OXIDIZED METHIONINE AND HAS DECREASED ELASTASE INHIBITORY CAPACITY
POTENTIAL MECHANISM OF EMPHYSEMA - ALPHA-1-PROTEINASE INHIBITOR RECOVERED FROM LUNGS OF CIGARETTE SMOKERS CONTAINS OXIDIZED METHIONINE AND HAS DECREASED ELASTASE INHIBITORY CAPACITY
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DOI：
10.1073/pnas.79.6.2041
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
JANOFF, A
中科院分区：
文献类型：
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作者：
CARP, H;MILLER, F;JANOFF, A
在来自26名健康吸烟者和24名非吸烟者的支气管肺泡灌洗液（BAL）中测量每毫克α 1-蛋白酶抑制剂（α 1 PI）的弹性蛋白酶抑制能力。与不吸烟者相比，吸烟者的BAL液活性降低了40%。通过使用人嗜中性粒细胞弹性蛋白酶和猪胰弹性蛋白酶作为测试酶弹性蛋白酶（EC 3.4.21.11）来证明这种效果，并且当每组中选择的个体重复进行灌洗时，这种效果是可再现的。α 1-抗胰凝乳蛋白酶的功能活性在吸烟者的BAL液中没有降低。交叉抗原-抗体电泳证实α 1 PI的失活是吸烟者BAL液弹性蛋白酶抑制能力降低的原因。从吸烟者的BAL液中纯化的α 1 PI含有甲硫氨酸亚砜（4 mol/mol无活性的α 1 PI）;从非吸烟者的BAL液中纯化的α 1 PI不含甲硫氨酸亚砜。基于电泳迁移率、MW和免疫反应性，吸烟者α 1 PI与非吸烟者α 1 PI是不可区分的。因此，肺α 1 PI中甲硫氨酸残基的氧化与吸烟有关。由于α 1 PI在体外的化学氧化导致其弹性蛋白酶抑制活性的丧失，甲硫氨酸氧化也可能是吸烟者肺α 1 PI功能活性降低的原因。吸烟者肺中α 1 PI的氧化失活可能在该组肺气肿的发展中起作用。
The elastase inhibitory capacity per milligram .alpha.1-proteinase inhibitor (.alpha.1PI) was measured in the bronchoalveolar lavage (BAL) fluid from 26 healthy smokers and 24 nonsmokers. Activity was decreased by 40% in smokers'' BAL fluid compared to nonsmokers. This effect was demonstrated by using human neutrophil elastase and porcine pancreatic elastase as test enzyme elastase, EC 3.4.21.11, and was reproducible when selected individuals in each group underwent lavage on repeated occasions. The functional activity of .alpha.1-antichymotrypsin was not decreased in smokers'' BAL fluid. Crossed antigen-antibody electrophoresis confirmed that inactivation of .alpha.1PI was responsible for the decrease in the elastase inhibitory capacity of smokers'' BAL fluid. .alpha.1PI purified from smokers'' BAL fluids contained methionine sulfoxide (4 mol/mol of inactive .alpha.1PI); .alpha.1PI from nonsmokers'' BAL fluid did not. Smokers'' .alpha.1PI was indistinguishable from nonsmokers'' .alpha.1PI on the basis of electrophoretic mobility, MW and immunoreactivity. Thus oxidation of methionine residues in lung .alpha.1PI was associated with cigarette smoking. Because chemical oxidation of .alpha.1PI in vitro caused loss of its elastase inhibitory activity, methionine oxidation may also be the cause of decreased functional activity of lung .alpha.1PI in smokers. Oxidative inactivation of .alpha.1PI in the lungs of cigarette smokers may play a role in the development of pulmonary epmphysema in this group.