ABSTRACT
One important physiological function of protein proteinase inhibitors is to prevent proteolysis operated by accidentally liberated proteinases. For instance, alpha 1proteinase inhibitor (alPI) and mucus proteinase inhibitor (MPI) (also called secretory leukoproteinase inhibitor) are thought to protect the lung tissue against the degrading action of neutrophil elastase (NE) (1). Protein proteinase inhibitors usually exhibit a good proteinase class specificity; e.g., serine proteinase inhibi tors do not inhibit cysteine or mettalloproteinases and vice versa. They are, however, poorly specific on an all-or-none basis. For instance, a lP I inhibits trypsin-like, chymotrypsin-like, and elastase-like serine proteinases in vitro (2). Because of this lack of specificity it is difficult to infer the physiological function of inhibitors from simple in vitro inhibition assays. Measurement of the kinetic constants characterizing the proteinase-inhibitor interaction and of the in vivo concentration of the inhibitor helps, however, to predict the proteolysis preventing function of an inhibitor. This chapter outlines the in vivo inhibition concept (3,4) and illustrates the theory with the NE/alPI and the NE/MPI systems.
