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.