Janoff A, White R, Carp H, Harel S, Dearing R, Lee D
Am J Pathol. 1979 Oct;97(1):111-36.
Human polymorphonuclear neutrophilic leukocytes (PMNs) contain large amounts of neutral proteases that can degrade elastin, collagen, proteoglycan, and basement membrane. The instillation of one of the purified enzymes (elastase) into dog lungs in vivo causes degradation of elastic fibers and other alveolar septal components and results in anatomic changes similar to those of human pulmonary emphysema. Cigarette smoking is a major risk factor associated with pulmonary emphysema in man. One mechanism for this association may be interference with the regulation of PMN elastase activity by alveolar antiproteases. This possibility is supported by the observation that the oxidizing activity of tobacco smoke inactivates alpha 1-proteinase inhibitor in vitro. Macrophages also secrete an elastolytic protease, albeit at low levels. The short-term exposure of cultured mouse macrophages to cigarette smoke augments the rate of elastase secretion by these cells. Mouse macrophage elastase is not inhibited by alpha 1-proteinase inhibitor or alpha 2-macroglobulin. This unusual property of macrophage elastase may facilitate its attack upon elastin over prolonged intervals despite very low levels of macrophage elastase production. A unified hypothesis of lung injury in pulmonary emphysema is presented, involving both PMN and macrophage elastases and the actions of cigarette smoke. (Am J Pathol 97:111--136, 1979).
人类多形核中性粒细胞（PMN）含有大量可降解弹性蛋白、胶原蛋白、蛋白聚糖和基底膜的中性蛋白酶。将其中一种纯化酶（弹性蛋白酶）体内注入犬肺会导致弹性纤维和其他肺泡隔成分降解，并产生与人类肺气肿相似的解剖学变化。吸烟是人类肺气肿的主要危险因素。这种关联的一种机制可能是肺泡抗蛋白酶对PMN弹性蛋白酶活性调节的干扰。体外观察到烟草烟雾的氧化活性使α1-蛋白酶抑制剂失活支持了这种可能性。巨噬细胞也分泌弹性溶解蛋白酶，尽管水平较低。培养的小鼠巨噬细胞短期暴露于香烟烟雾会增加这些细胞的弹性蛋白酶分泌速率。小鼠巨噬细胞弹性蛋白酶不受α1-蛋白酶抑制剂或α2-巨球蛋白抑制。巨噬细胞弹性蛋白酶的这种不寻常特性可能有助于其在很长一段时间内对弹性蛋白的攻击，尽管巨噬细胞弹性蛋白酶的产生水平非常低。本文提出了一个关于肺气肿肺损伤的统一假说，涉及PMN和巨噬细胞弹性蛋白酶以及香烟烟雾的作用。（《美国病理学杂志》97:111 - 136，1979年）
