Inhibition of neutrophil elastase by the α1-proteinase inhibitor-immunoglobulin A complex

Abstract

Neutrophil elastase is thought to be involved in cartilage destruction occurring in rheumatoid arthritis despite the local presence of α 1-proteinase inhibitor. Part of synovial fluid α 1-proteinase inhibitor forms a mixed disulfide with immunoglobulin A, which has been postulated to lack inhibitory activity. We show here that the immunoglobulin-inhibitor complex tightly inhibits neutrophil elastase and cathepsin G, bovine pancreatic trypsin and chymotrypsin, and porcine pancreatic elastase. Although the rate constant of inhibition of neutrophil elastase by immunoglobulin A-bound α 1-proteinase inhibitor ( k ass = 9.2 × 10 5 M −1 · s −1) is about 10-fold lower than that measured with the free inhibitor, it is high enough to enable efficient inhibition of elastase in vivo.