Cathepsin G Inactivates Human Protein S in vitro

Abstract

Human polymorphonuclear leukocyte cathepsin G was used in vitro to digest human protein S. While clotting assays indicated that the proteinase induced a rapid decrease in activity, polyacrylamide gel electrophoresis-sodium dodecyl sulphate indicated the removal of a peptide of low molecular mass product protein S (des 1-40). The loss in activity was the result of cathepsin G cleaving position Phe40-Tyr41 and removing the calcium-binding region. Calcium ions almost totally protected the cofactor from the action of cathepsin G in vitro.

The Anticoagulant Potential of the Protein C System in Hereditary and Acquired Thrombophilia: Pathomechanisms and New Tools for Assessing its Clinical Relevance

“…62 Disturbances of the PC system may also be caused by leukocyte-derived proteases released at the inflamed site. It has been shown in vitro, that elastase and cathepsin G degrade the γ-carboxylated binding sites of PS and PC, both thereby losing their ability to bind to phospho lipid surfaces and to inactivate factors Villa and Va. 63,64 In lung cancer, elastase-inhibitor complexes and the loss of clotting activity of PC have been the only parameters that correlated with the state of the disease. In contrast, the ability of PC to cleave a chromogenic substrate was unchanged.…”