Elastin Degradation in Human and Experimental Emphysema
It has been postulated that elastolytic breakdown of pulmonary connective tissue is the primary insult leading to emphysematous lesions in patients and experimental animals. In support of this mechanism we show (1) by biochemical analysis — that elastin content of connective tissue has been decreased in the parenchyma of emphysematous human subjects compared to normal human controls and in rats receiving 20 mg pancreatic elastase i.v. (2) by electron microscopy — that amorphous elastin is the only component of the pulmonary tissue reduced in the early stages of emphysema (3) immunologically — that enzymatic breakdown products of human lung elastin give rise to specific antibodies in the circulation of experimental animals (rabbits) and may stimulate antibodies in patients with pulmonary emphysema. The enzymes responsible for degradation of pulmonary elastin have not been established but three possibilities will be discussed: Polymorphonuclear leukocyte elastase which in phenotypical ly normal (α1-antitrypsin) MM subjects has been found to be present in statistically significantly higher amounts in patients with emphysema as compared with normal human subjects (2) alveolar macrophage elastase (3) specific tissue elastases. Work in progress is designed to distinguish the peptides resulting from digestion of human lung elastin by these enzymes on the basis of differences in their precipitating anti bodies.
KeywordsPulmonary Emphysema Entire Lung Leukocyte Elastase Pancreatic Elastase Elastin Content
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