Interaction of human alpha 1-proteinase inhibitor with human leukocyte cathepsin G.

Abstract

Interaction of human plasma alpha 1-proteinase inhibitor (alpha 1-PI) with human leukocyte cathepsin G was assessed by proteinase inhibitory capacity assays and electrophoretic analyses. Only a part of purified alpha 1-PI formed a 1 : 1 complex (Mr = 74 000) with leukocyte cathepsin G. The formation of this complex was accompanied by the appearance of a great amount of a free, proteolytically modified form of alpha 1-PI (Mr = 50 000) which had lost its inhibitory capacity. The complex was unstable with time and the only dead end product observed was a modified, inactive form of alpha 1-PI. During the breakdown of the complex, no release of active enzyme could be measured by spectrophotometric assays. In spite of the fact that the equimolarity of the complex was convincingly demonstrated, studies of the alpha 1-PI-cathepsin G reaction showed that total inhibition of this proteinase needed a large molar excess of alpha 1-PI. Nevertheless, alpha 1-PI acts as an efficient "suicide inhibitor" since no cathepsin G recovery was ever found.