Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype. Evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha 1-proteinase inhibitor.
Plasma levels of elastase-specific fibrinopeptides correlate with proteinase inhibitor phenotype. Evidence for increased elastase activity in subjects with homozygous and heterozygous deficiency of alpha 1-proteinase inhibitor.
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弹性蛋白酶特异性纤维蛋白肽的血浆水平与蛋白酶抑制剂表型相关。
DOI：
10.1172/jci115654
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Campbell,EJ
中科院分区：
文献类型：
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作者：
Weitz,JI;Silverman,EK;Thong,B;Campbell,EJ
有间接证据表明，非对抗性的人中性粒细胞弹性蛋白酶（HNE）是负责与α 1-蛋白酶抑制剂（Pi）缺乏症患者的肺气肿。为了直接探索这种可能性，我们开发了一种测定纤维蛋白肽A α 1-21及其降解产物的方法，并用它来测量128名已知Pi表型受试者的HNE活性。49例PiZ缺陷型个体的弹性蛋白酶特异性纤维蛋白肽（ESF）水平显著高于56例PiMZ杂合子（分别为4.5和1.5 nM; P <0.01），而杂合子的平均ESF值显著高于23名正常PiM受试者（分别为1.5和0.6 nM; P小于0.01），这与酶的主要调节因子缺乏的人中HNE活性增加一致。这些结果不是由于吸烟史的差异，因为校正吸烟包年后，PiZ受试者的ESF值比PiMZ个体高4倍（P = 0.005），而杂合子的ESF水平比PiM受试者高3倍（P = 0.02）。此外，这项分析表明，吸烟和α 1-蛋白酶抑制剂缺乏对ESF水平有累加效应，从而解释了为什么PiZ和一些PiMZ个体如果吸烟，患肺病的风险特别高。最后，非吸烟PiZ受试者的ESF水平与1秒用力呼气量预测值（FEV 1%）的百分比呈负相关，这一观察结果直接支持了α 1蛋白酶抑制剂缺乏症患者中HNE活性不受调节导致肺泡间隔破坏的概念。
There is indirect evidence that unopposed human neutrophil elastase (HNE) is responsible for emphysema in patients with alpha 1-proteinase inhibitor (Pi) deficiency. To directly explore this possibility, we developed an assay for fibrinopeptide A alpha 1-21 and its degradation products and used it to measure HNE activity in 128 subjects of known Pi phenotype. The mean elastase-specific fibrinopeptide (ESF) level in 49 deficient PiZ individuals is significantly higher than that in 56 PiMZ heterozygotes (4.5 and 1.5 nM, respectively; P less than 0.01), while the mean ESF value in heterozygotes is significantly elevated over that in 23 normal PiM subjects (1.5 and 0.6 nM, respectively; P less than 0.01), consistent with increased HNE activity in those deficient in the major regulator of the enzyme. These results are not due to differences in smoking history because after correction for pack-years of smoking, ESF values in PiZ subjects are fourfold higher than those in PiMZ individuals (P = 0.005), while the ESF levels in heterozygotes are threefold higher than those in PiM subjects (P = 0.02). In addition, this analysis suggests that cigarette smoking and alpha 1-proteinase inhibitor deficiency have additive effects on ESF levels thereby explaining why PiZ and some PiMZ individuals are at especially high risk for the development of lung disease if they smoke. Finally, the observation that ESF levels in nonsmoking PiZ subjects are inversely related to the percent of predicted forced expiratory volume in 1 s (FEV 1%) provides direct support for the concept that unregulated HNE activity causes alveolar septal destruction in patients with alpha 1-proteinase inhibitor deficiency.