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.