Bronchial leukocyte proteinase inhibitor: hydrodynamic properties and interaction with alpha 2-macroglobulin-bound elastase

Abstract

Bronchial leukocyte proteinase inhibitor (BLPI) is an 11.7 kDa, acid-stable protein found in mucous secretions, which inhibits neutrophil elastase. The Stoke's radius of BLPI calculated from sedimentation equilibrium and sedimentation velocity centrifugation data was in good agreement with the value determined by gel filtration. These data indicate that BLPI exists in a compact globular conformation at both neutral and acidic pH. BLPI, due to its small compact size, can inhibit neutrophil elastase after the enzyme has been complexed with alpha 2-macroglobulin (A-2-M) but alpha 1-proteinase inhibitor failed to inactivate A-2-M-bound elastase. The apparent association rates of BLPI and Eglin C with A-2-M-bound elastase were found to be 6.3 X 10(2) M-1s-1 and 1.1 X 10(3) M-1s-1, respectively. These apparent association rates decreased 168-fold for BLPI and 909-fold for Eglin C, relative to the association rates of these inhibitors with free elastase. These changes probably result from a combination of effects, such as inhibitor accessibility to the enzyme and/or reaction rate, but regardless of the mechanism these data suggest that BLPI may function to control both free and A-2-M-bound elastase.