Bieth J G
INSERM U 237, Université Louis-Pasteur de Strasbourg, Faculté de Pharmacie, Illkirch, France.
Pathol Biol (Paris). 1988 Nov;36(9):1108-11.
This article reviews some properties of human leucocyte elastase. This 30 kDa glycoprotein formed of 218 amino acid residues, is a serine proteinase which cleaves proteins at Val-X, Ala-X, Leu-X or Met-X bonds. Leucocyte elastase solubilizes fibrous elastin and also degrades other extracellular matrix proteins. It hydrolyses and inactivates a number of plasma proteins. Synthetic substrates are more convenient than elastin to measure elastase activity. A large number of natural and synthetic inhibitors of leucocyte elastase have been described. The former include alpha 1-proteinase inhibitor or alpha 1-antitrypsin, inter-alpha-inhibitor, alpha 2-macroglobulin, bronchial and cervical mucous inhibitor and a number of animal and plant proteins. Numerous synthetic inhibitors with therapeutic potentials have been designed. The efficiency of an inhibitor depends, among others, upon its rate of association with the enzyme and upon the stability of the enzyme-inhibitor complex. Elastase probably plays a physiological function in neutrophil migration, phagocytosis and tissue remodeling. It apparently plays a pathological role in pulmonary emphysema, rheumatoid arthritis, infections and inflammation. The pathogenic role of leucocyte elastase is best understood in emphysema.
本文综述了人白细胞弹性蛋白酶的一些特性。这种由218个氨基酸残基组成的30 kDa糖蛋白是一种丝氨酸蛋白酶，可在Val-X、Ala-X、Leu-X或Met-X键处切割蛋白质。白细胞弹性蛋白酶可溶解纤维弹性蛋白，还能降解其他细胞外基质蛋白。它能水解并使多种血浆蛋白失活。合成底物比弹性蛋白更便于测量弹性蛋白酶活性。已描述了大量白细胞弹性蛋白酶的天然和合成抑制剂。前者包括α1-蛋白酶抑制剂或α1-抗胰蛋白酶、α-间抑制剂、α2-巨球蛋白、支气管和宫颈黏液抑制剂以及一些动植物蛋白。已设计出许多具有治疗潜力的合成抑制剂。抑制剂的效率尤其取决于其与酶的结合速率以及酶-抑制剂复合物的稳定性。弹性蛋白酶可能在中性粒细胞迁移、吞噬作用和组织重塑中发挥生理功能。它显然在肺气肿、类风湿性关节炎、感染和炎症中起病理作用。白细胞弹性蛋白酶在肺气肿中的致病作用最为人所熟知。
