Eglin-c, a Polypeptide Derived from the Medicinal Leech, Prevents Human Neutrophil Elastase-Induced Emphysema and Bronchial Secretory Cell Metaplasia in the Hamster1–3

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 × 10×10 moles of human neutrophil elastase (HNE) with 3H-elastin in the presence of 8.2 × 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-Egc-HNE complex. In vivo studies were carried out in weight-matched groups of anesthetized golden Syrian hamsters given 100, 300, 500, or 2,000 μg of Eg-c in 0.5 ml saline intratracheally 1 h before 300 μg HNE was administered intratracheally. Control animals received saline followed by HNE or 2 doses of saline 1 h apart. Eight weeks later, lung s...