Eglin-c, a polypeptide derived from the medicinal leech, prevents human neutrophil elastase-induced emphysema and bronchial secretory cell metaplasia in the hamster.
Eglin-c (Eg-c), a polypeptide with a molecular mass of 8,100 daltons, was purified from the medicinal leech Hirudo medicinalis. The Eg-c was tritiated by reductive methylation for in vitro studies. Incubation of 2.1 X 10(-10) moles of human neutrophil elastase (HNE) with 3H-elastin in the presence of 8.2 X 10(-10) moles of 3H-Eg-c inhibited 98.7% of the elastolytic activity of the enzyme. Using Sephadex G 100 chromatography and 1.7 moles of 3H-Eg-c per mole of HNE, a 34,000-dalton complex (3H-Eg-c-HNE) was observed. The stability of the complex formed between 3H-Eg-c and HNE that had been inactivated with succinyl-ala2-pro-val CH2Cl was much less than that of the 3H-Eg-c-HNE complex. In vivo studies were carried out in weight-matched groups of anesthetized golden Syrian hamsters given 100, 300, 500, or 2,000 micrograms of Eg-c in 0.5 ml saline intratracheally 1 h before 300 micrograms HNE was administered intratracheally. Control animals received saline followed by HNE or 2 doses of saline 1 h apart. Eight weeks later, lung statics and dynamics were measured in anesthetized animals, followed by histologic study of lung parenchyma and the mucosa of the large intrapulmonary airways. There were no deaths, and final mean body weights were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001980:Bronchi / Q000473:pathology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004646:Emphysema / Q000139:chemically induced / Q000517:prevention & control*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007865:Leeches / Q000032:analysis; D008170:Lung Compliance; D008176:Lung Volume Measurements; D008297:Male; D008647:Mesocricetus; D008679:Metaplasia / Q000139:chemically induced; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000009:adverse effects / Q000097:blood; D011480:Protease Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D015843:Serpins
D011480:Protease Inhibitors; D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D010196:Pancreatic Elastase