Ogushi F, Hubbard R C, Vogelmeier C, Fells G A, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1991 Mar;87(3):1060-5. doi: 10.1172/JCI115066.
The increased risk of developing emphysema among individuals who smoke cigarettes and who have normal levels of alpha 1-antitrypsin (alpha 1AT) is hypothesized to result from a decrease in the antineutrophil elastase capacity of the lower respiratory tract alpha 1AT of smokers compared with nonsmokers. To evaluate this hypothesis we compared the time-dependent kinetics of the inhibition of neutrophil elastase by lung alpha 1AT from healthy, young cigarette smokers (n = 8) and nonsmokers (n = 12). alpha 1-antitrypsin was purified from lavage fluid using affinity and molecular sieve chromatography, and the association rate constant (k assoc) for neutrophil elastase quantified. The k assoc of smoker plasma alpha 1AT (9.5 +/- 0.5 X 10(6) M-1s-1) was similar to that of nonsmoker plasma (9.3 +/- 0.7 X 10(6) M-1s-1, P greater than 0.5). In marked contrast, the k assoc of smoker lower respiratory tract alpha 1AT was significantly lower than that of nonsmoker alpha 1AT (6.5 +/- 0.4 X 10(6) M-1s-1 vs. 8.1 +/- 0.5 X 10(6) M-1s-1, P less than 0.01). Furthermore, the smoker lower respiratory tract alpha 1AT k assoc was significantly less than that of autologous plasma (P less than 0.01). When considered in the context of the concentration of alpha 1AT in the lower respiratory tract epithelial lining fluid, the inhibition time for neutrophil elastase of smoker lung alpha 1AT was twofold greater than that of nonsmoker lung alpha 1AT (smoker: 0.34 +/- 0.05 s vs. nonsmoker: 0.17 +/- 0.05 s, P less than 0.01). Consequently, for concentrations of alpha 1AT in the lower respiratory tract it takes twice as long for an equivalent amount of neutrophil elastase to be inhibited in the smoker's lung compared with the nonsmoker's lung. These observations support the concept that cigarette smoking is associated with a decrease in the lower respiratory tract neutrophil elastase inhibitory capacity, thus increasing the vulnerability of the lung to elastolytic destruction and thereby increasing the risk for the development of emphysema.
据推测，吸烟且α1 -抗胰蛋白酶（α1AT）水平正常的个体患肺气肿风险增加，是因为与不吸烟者相比，吸烟者下呼吸道α1AT的抗中性粒细胞弹性蛋白酶能力降低。为评估这一假设，我们比较了健康年轻吸烟者（n = 8）和不吸烟者（n = 12）肺α1AT对中性粒细胞弹性蛋白酶抑制作用的时间依赖性动力学。使用亲和色谱和分子筛色谱从灌洗液中纯化α1 -抗胰蛋白酶，并对中性粒细胞弹性蛋白酶的缔合速率常数（k assoc）进行定量。吸烟者血浆α1AT的k assoc（9.5±0.5×10⁶ M⁻¹s⁻¹）与不吸烟者血浆的k assoc（9.3±0.7×10⁶ M⁻¹s⁻¹，P＞0.5）相似。形成显著对比的是，吸烟者下呼吸道α1AT的k assoc显著低于不吸烟者的α1AT（6.5±0.4×10⁶ M⁻¹s⁻¹对8.1±0.5×10⁶ M⁻¹s⁻¹，P＜0.01）。此外，吸烟者下呼吸道α1AT的k assoc显著低于自体血浆的k assoc（P＜0.01）。结合下呼吸道上皮衬液中α1AT的浓度来看，吸烟者肺α1AT对中性粒细胞弹性蛋白酶的抑制时间是不吸烟者肺α1AT的两倍（吸烟者：0.34±0.05秒对不吸烟者：0.17±0.05秒，P＜0.01）。因此，对于下呼吸道中相同浓度的α1AT，与不吸烟者的肺相比，等量的中性粒细胞弹性蛋白酶在吸烟者的肺中被抑制所需的时间要长两倍。这些观察结果支持了这样一种观点，即吸烟与下呼吸道中性粒细胞弹性蛋白酶抑制能力降低有关，从而增加了肺对弹性蛋白溶解破坏的易感性，进而增加了患肺气肿的风险。
