Effect of varying the time interval between intratracheal administration of eglin-c and human neutrophil elastase on prevention of emphysema and secretory cell metaplasia in hamsters. With observations on the fate of eglin-c and the effect of repeated instillations.
Eglin-c is a naturally occurring polypeptide of 70 amino acids with a molecular mass of 8,100 daltons. It is a strong inhibitor of human neutrophil elastase (HNE) and cathepsin-G, and, when given intratracheally to hamsters 1 h before human neutrophil elastase, it can prevent or ameliorate the emphysema produced by HNE. The present experiments were designed to determine the duration of the effectiveness of eglin-c, prepared by DNA technology from Escherichia coli, in preventing the emphysema and secretory cell metaplasia induced by HNE. Eglin-c (2,000 micrograms in 0.5 ml saline) was effective in ameliorating emphysema, as determined histologically and physiologically, when it was given intratracheally to hamsters 1, 2, 4, and 8 h before the intratracheal instillation of 300 micrograms of HNE. Eglin-c ameliorated bronchial secretory cell metaplasia when given 1 h before HNE but not when the time intervals were 2 h or longer. The clearance of [3H]eglin-c from the lungs was assessed. Four h after intratracheal instillation of 446 micrograms of [3H]eglin-c, 33% of the tritium was found in the lung tissue and bronchoalveolar lavage fluid; 83% of the radioactivity in the lavage fluid supernatant was associated with functionally active eglin-c. No evidence of bronchopulmonary toxicity was seen in hamsters given 4 intratracheal instillations of 2,000 micrograms of eglin-c at 1-wk intervals.
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D008679:Metaplasia; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000633:toxicity; D011480:Protease Inhibitors / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015843:Serpins; D014132:Trachea
D011480:Protease Inhibitors; D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D010196:Pancreatic Elastase