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, a polypeptide derived from the medicinal leech, prevents human neutrophil elastase-induced emphysema and bronchial secretory cell metaplasia in the hamster.
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DOI:
10.1164/arrd.1985.132.6.1155
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发表时间:
1985-12
期刊:
The American review of respiratory disease
影响因子:
--
通讯作者:
G. Snider;P. Stone;E. Lucey;R. Breuer;J. Calore;T. Seshadri;A. Catanese;R. Maschler;H. Schnebli
G. Snider;P. Stone;E. Lucey;R. Breuer;J. Calore;T. Seshadri;A. Catanese;R. Maschler;H. Schnebli
中科院分区:
其他
文献类型:
--
作者:
G. Snider;P. Stone;E. Lucey;R. Breuer;J. Calore;T. Seshadri;A. Catanese;R. Maschler;H. Schnebli

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Eglin-c(Eg-c)是从药用水蛭水蛭(Hirudo medicine)中纯化的一种多肽,分子量为8,100道尔顿。Eg-c通过还原甲基化进行氚化用于体外研究。在8.2 × 10 ~(-10)mol ~ 3 H-Eg-c存在下,2.1 × 10 ~(-10)mol人中性粒细胞弹性蛋白酶(HNE)与~ 3 H-弹性蛋白孵育抑制98.7%的酶的弹性蛋白溶解活性。用Sephadex G 100层析和每摩尔HNE 1.7摩尔的3 H-Eg-c,观察到34,000-道尔顿复合物(3 H-Eg-c-HNE)。经琥珀酰-丙氨酸2-脯氨酸-CH_2Cl灭活的HNE与~ 3 H-Eg-c形成的复合物的稳定性远低于~ 3 H-Eg-c-HNE复合物。在体重匹配的麻醉金黄色叙利亚仓鼠组中进行体内研究,在300微克HNE气管内给药前1小时,气管内给予100、300、500或2,000微克Eg-c的0.5 ml盐水溶液。对照组动物接受生理盐水,然后接受HNE或间隔1小时的2次生理盐水给药。8周后,在麻醉动物中测量肺静态和动态,然后对肺实质和肺内大气道的粘膜进行组织学研究。无死亡,所有组的最终平均体重相似。(250字处删节)
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)