Compromised inhibition of human lung lavage cell elastases

FEBS Letters

Guz, A.¹  Smith, S.F.¹  Tetley, T.D.¹  Roberts, N.A.² 

[1] Department of Medicine, Charing Cross and Westminster Medical School, Fulham Palace Road, London W6 8RF, UK;Department of Biology, Roche Products Limited, P.O. Box 8, Welwyn Garden City, Herts. AL7 3AY, UK

关键词: Bronchoalveolar lavage;    Neutrophil elastase;    α-1-Proteinase inhibitor;    Matrix metalloproteinases;    Alveolar macrophage;    MMP;    matrix metalloproteinase;    BAL;    bronchoalveolar lavage;    Ro 31-3537;    N ϵ-(l-adamantanesulphonyl)-N ϵ-(4-carboxybenzoyl)-l-lysyl-l-alanyl-l-valinal;    DMEM;    Dulbecco's modified Eagle's medium;    LPHM;    low protein hybridoma medium;    PI;    α-1-proteinase inhibitor;   

DOI  :  10.1016/0014-5793(96)00655-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Increased elastinolytic activity has been correlated with the degree of lung damage occurring in a variety of lung diseases including cystic fibrosis; serine proteinase inhibitors are currently on trial for the treatment of some lung disorders. However, human lung lavage cells also secrete metallo-dependent elastases. Here we show, for the first time, that whilst these are readily inhibited by EDTA, inhibition of serine elastases using serpins (serine proteinase inhibitors) is not always possible. This may reflect inactivation of serpins by uninhibited metalloproteinases and oxidants in a low protein milieu. Thus, the therapeutic inhibition of excessive elastinolytic activity may require a combination of inhibitors to work efficiently.

【 授权许可】

Unknown