Putative role of neutrophil elastase in the pathogenesis of emphysema.
Emphysema in humans takes several different forms: centrilobular, panacinar, paraseptal, and airspace enlargement with fibrosis. The varying morphologic and background features of these forms of emphysema suggest that they differ in pathogenesis. Elastic fiber rupture and fraying are a feature of emphysema. Experimental emphysema may be induced by human neutrophil elastase and other elastolytic enzymes but not by nonelastolytic proteases. Disruption of elastic fibers also appears to be the underlying feature of lathyrogen-induced airspace enlargement and of the emphysema in the blotchy mouse. However, there is no evidence of elastic fiber destruction in cadmium-induced airspace enlargement with fibrosis or in emphysema associated with hyperoxia or severe starvation. Thus, elastic fiber disruption is not common to all forms of experimental emphysema. We posit that airspace enlargement may be a stereotyped response of the lungs to different injuries. Emphysema can be induced in experimental animals by repeated induction of pulmonary neutrophilia. However, the evidence for involvement of neutrophil elastase in human emphysema is not clear: there are studies using a variety of approaches that weigh on both sides of the question. There is also in vitro evidence that alveolar macrophages can degrade elastin or elastic fibers with which they are in contact by means of a metalloelastase or the cooperative action of plasminogen activator and an acid cysteine protease. We conclude that the pathogenesis of emphysema is complex. Neutrophil elastase likely plays a major role in the development of some forms of emphysema, but our understanding of the interactions between the alveolar walls and neutrophils is still fragmentary.
Snider
G L
GL
Pulmonary Center, Boston University School of Medicine, Massachusetts.
Ciccolella
D E
DE
Morris
S M
SM
Stone
P J
PJ
Lucey
E C
EC
D000818:Animals; D002104:Cadmium / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D019272:Leukocyte Elastase; D008168:Lung / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000032:analysis / Q000502:physiology*; D011656:Pulmonary Emphysema / Q000209:etiology*
D002104:Cadmium; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase