The degradation of human lung elastin by neutrophil proteinases.
Human lung elastin has been isolated by both a degradative and nondegradative procedure and the products obtained found to have amino acid compositions comparable to published results. These elastin preparations, when utilized as substrates for various mammalian proteinases, were solubilized by porcine elastase at a rate six times faster than human leukocyte elastase. Leukocyte cathepsin G also solubilized lung elastin but only at 12% of the rate of the leukocyte elastase. In all cases the elastin prepared by nondegradative techniques proved to be the best substrate in these studies. The differences in the rate of digestion of elastin of the two elastolytic proteinases was readily attributed to the specificity differences of each enzyme as judged by carboxyterminal analysis of solubilized elastin peptides. The plasma proteinase inhibitors, alpha-1-proteinase inhibitor and alpha-2-macroglobulin abolished the elastolytic activity of both leukocyte enzymes, while alpha-1-antichymotrypsin specifically inactivated cathespsin G. Two synthetic inhibitors, Me-O-Suc-Ala-Ala-Pro-Val-CH2Cl (for elastase and Z-Gly-Leu-Phe-CH2Cl (for cathepsin G) were equally effective in abolishing the elastolytic activity of the two neutrophil enzymes. However, inhibition of leukocyte elastase by alpha-1-proteinase inhibitor was significantly suppressed if the enzyme was preincubated with elastin prior to addition of the inhibitor.
D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002918:Chymotrypsin / Q000378:metabolism; D004549:Elastin / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008722:Methods; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D014361:Trypsin Inhibitors / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000494:pharmacology
D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D004549:Elastin; D002403:Cathepsins; D002918:Chymotrypsin; D010196:Pancreatic Elastase