The Induction of Pulmonary Emphysema with Human Leukocyte Elastase^1–3

Abstract

Purified human leukocyte elastase was injected into the tracheas of 46 hamsters. Thirteen animals died spontaneously within 1 week, with extensive lung hemorrhage. The elastin content of the lungs was only slightly less than control values 3 hours after injection. At 2 months, the lungs of the remaining animals showed mild, patchy emphysema and morphometric changes consistent with emphysema. These results contrasted with the effects of a similar elastolytic dose of pancreatic elastase administered to 26 other hamsters in that only one animal died spontaneously, the lung elastin content 3 hours after injection was substantially decreased, and severe emphysema was present 2 months later. Leukocyte elastase appears to be capable of causing emphysema; but unlike pancreatic elastase, leukocyte elastase produces emphysema that is mild, even at a dose sufficient to produce intense lung hemorrhage and a high mortality.

Smoke Extract Stimulates Lung Epithelial Cells to Release Neutrophil and Monocyte Chemotactic Activity

“…29 -31 Anti-LTB 4 serum, [5,6,8,9,11,12,14,15,3 H(N)]-LTB 4 , and synthetic LTB 4 were purchased from Amersham Co. (Arlington Heights, IL). Briefly, ethanol and supernatant mixtures were centrifuged at 5500 ϫ g at 0°C.…”

“…8 Senior and co-workers reported that experimental emphysema was induced by intratracheal instillation of purified human neutrophil elastase in animals. 9 Thus, the cigarette smoke may influence both matrix damage and repair processes, leading to lung destruction by inflammatory processes.…”

Alpha One Antitrypsin Deficiency: A Pulmonary Genetic Disorder

“…Neutrophil elastase was shown to induce experimental emphysema in animals. (Senior, et al 1977). These findings lead to the first hypothesis describing the pathogenesis of lung disease, that an imbalance of proteases and anti-proteases could result in an unregulated destruction of critical components of lung structure, namely elastin, leading to the development of clinical lung disease.…”

Albumin microspheres as carrier of an inhibitor of leukocyte elastase: potential therapeutic agent for emphysema.

“…It may be furthermore noted from Fig. 3 that approximately 40 (20,21), it should be possible to demonstrate whether inhibitor-bearing microspheres can in fact prevent the development of emphysema without undue damage to the animal.…”