ANTI-ELASTASES OF THE HUMAN ALVEOLAR STRUCTURES - IMPLICATIONS FOR THE PROTEASE-ANTIPROTEASE THEORY OF EMPHYSEMA
ANTI-ELASTASES OF THE HUMAN ALVEOLAR STRUCTURES - IMPLICATIONS FOR THE PROTEASE-ANTIPROTEASE THEORY OF EMPHYSEMA
复制标题
DOI：
10.1172/jci110344
复制
发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
CRYSTAL, RG
中科院分区：
文献类型：
--
作者：
GADEK, JE;FELLS, GA;CRYSTAL, RG
肺泡结构的进行性慢性破坏显然是由于下呼吸道中蛋白酶和抗蛋白酶之间的不平衡而发生的。在这种情况下，蛋白酶，特别是中性粒细胞弹性蛋白酶，不受阻碍地破坏肺泡结构。这一概念是从考虑患有α 1-抗胰蛋白酶缺乏的患者发展而来的，这些患者血清α 1-抗胰蛋白酶水平降低，并且患有进行性全腺泡肺气肿。为了直接评估该等式的抗蛋白酶方面，对具有正常血清抗蛋白酶的非吸烟个体和具有PiZ纯合α 1-抗胰蛋白酶缺乏的个体的下呼吸道进行支气管肺泡灌洗以评估其下呼吸道的抗蛋白酶筛选。α 1-抗胰蛋白酶是正常人下呼吸道的主要抗弹性蛋白酶。α 2-巨球蛋白（一种大的血清抗弹性蛋白酶）和支气管粘液抑制剂（一种中央气道的抗弹性蛋白酶）对人肺泡结构的抗弹性蛋白酶保护没有贡献。PiZ α 1-抗胰蛋白酶缺乏的个体在其下呼吸道中几乎没有或没有α 1-抗胰蛋白酶，并且没有针对嗜中性粒细胞弹性蛋白酶的替代性抗蛋白酶保护。PiZ个体的下呼吸道缺乏抗蛋白酶保护是一个慢性过程，这表明他们对中性粒细胞弹性蛋白酶的脆弱性始终存在。
Progressive, chronic destruction of the alveolar structures apparently occurs because there is an imbalance between the proteases and antiproteases in the lower respiratory tract. In this context, proteases, particularly neutrophil elastase, work unimpeded to destroy the alveolar structures. This concept has evolved from consideration of patients with .alpha.1-antitrypsin deficiency, who have decreased levels of serum .alpha.1-antitrypsin and who have progressive panacinar emphysema. To directly assess the antiprotease side of this equation, the lower respiratory tract of nonsmoking individuals with normal serum antiproteases and individuals with PiZ homozygous .alpha.1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract. .alpha.1-Antitrypsin is the major antielastase of the normal human lower respiratory tract. .alpha.2-Macroglobulin, a large serum antielastase, and the bronchial mucous inhibitor, an antielastase of the central airways, do not contribute to the antielastase protection of the human alveolar structures. Individuals with PiZ .alpha.1-antitrypsin deficiency have little or no .alpha.1-antitrypsin in their lower respiratory tract and have no alternative antiprotease protection against neutrophil elastase. The lack of antiprotease protection of the lower respiratory tract of PiZ individuals is a chronic process, suggesting that their vulnerability to neutrophil elastase is always present.