COMPROMISED INHIBITION OF HUMAN LUNG LAVAGE CELL ELASTASES

Increased elastinolytic activity has been correlated with the degree o f 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 al so secrete metallo-dependent elastases, Here we show, for the first ti me, that whilst these are readily inhibited by EDTA, inhibition of ser ine elastases using serpins (serine proteinase inhibitors) is not alwa ys possible, This may reflect inactivation of serpins by uninhibited m etalloproteinases and oxidants in a low protein milieu. Thus, the ther apeutic inhibition of excessive elastinolytic activity may require a c ombination of inhibitors to work efficiently.