Stone P J, Pereira W, Biles D, Snider G L, Kagan H M, Franzblau C
Am Rev Respir Dis. 1977 Jul;116(1):49-56. doi: 10.1164/arrd.1977.116.1.49.
Intratracheal instillation of pancreatic elastase in hamsters produces emphysema, which progresses for up to one year after the insult. To study this process in more detail, a guanidinated derivative of porcine pancreatic elastase labeled with carbon-14 was prepared that was indistinguishable from unmodified elastase with respect to physicochemical properties and in vitro enzymatic activity. Guanidinated pancreatic elastase exhibits the same emphysema-inducing potency as unmodified pancreatic elastase. Two hours after intratracheal instillation of the [14C] guanidinated elastase, the whole lung retained only 40 per cent of the instilled radioactivity, but after 96 hours one per cent was still present. At 2 hours approximately 90 per cent of the radioactivity in the lungs could be removed by bronchopulmonary lavage, and at 96 hours 28 per cent was removable by this method. More than half of the radiolabeled elastase recovered in the lavage fluid at 2 hours was enzymatically active; enzymatic activity diminished to very small amounts by 96 hours. These data support the concept of the long-term binding of active elastase to lung tissue, a phenomenon that may be involved in the progressive nature of elastase-induced emphysema.
给仓鼠气管内注入胰弹性蛋白酶可导致肺气肿，在损伤后这种肺气肿可持续发展长达一年。为了更详细地研究这一过程，制备了一种用碳-14标记的猪胰弹性蛋白酶的胍基化衍生物，其物理化学性质和体外酶活性与未修饰的弹性蛋白酶无异。胍基化胰弹性蛋白酶与未修饰的胰弹性蛋白酶具有相同的诱发肺气肿的能力。气管内注入[14C]胍基化弹性蛋白酶两小时后，整个肺仅保留了注入放射性的40%，但96小时后仍有1%存在。两小时时，肺内约90%的放射性可通过支气管肺灌洗去除，96小时时，该方法可去除28%。两小时时灌洗液中回收的放射性标记弹性蛋白酶一半以上具有酶活性；到96小时时，酶活性降至非常低的水平。这些数据支持活性弹性蛋白酶与肺组织长期结合的概念，这一现象可能与弹性蛋白酶诱导的肺气肿的进展性质有关。
