Inhibition of neutrophil elastase by the alpha1-proteinase inhibitor-immunoglobulin A complex

Neutrophil elastase is thought to be involved in cartilage destruction occurring in rheumatoid arthritis despite the local presence of alpha1-proteinase inhibitor. Part of synovial fluid alpha1-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 alpha1-proteinase inhibitor (k(ass) = 9.2 X 10(5) M(-1) x 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.