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.
Adam
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Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, Illkirch, France.
Bieth
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JG
D015153:Blotting, Western; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002850:Chromatography, Gel; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D019272:Leukocyte Elastase; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D012697:Serine Endopeptidases; D014361:Trypsin Inhibitors / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism / Q000494:pharmacology*
D007070:Immunoglobulin A; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D002403:Cathepsins; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase