Interaction of granulocyte proteases with inhibitors in pulmonary diseases.
The elastase-antielastase hypothesis of lung tissue destruction has focused our interest on the two main inhibitors of granulocyte elastase in the lung, alpha 1-antitrypsin dominating blood, interstitial tissue and alveolar fluid lining and antileukoprotease dominating the respiratory tract mucosa. Antileukoprotease as well as elastase and alpha 1-antitrypsin show increased serum levels during bronchitis and bronchopneumonia, alpha 1-antitrypsin because it is an acute phase reactant, elastase and antileukoprotease because of influx from the inflamed tissues. Elastase is identified in the bronchial expectorates, mainly in complex with antileukoprotease, but often also in a free, active form. The granulocyte elastase in serum from these patients is, however, only found in complex with alpha 1-antitrypsin. The increased amounts of antileukoprotease in serum are always in a free and largely active form. The explanation for the absence of elastase-antileukoprotease complexes in serum is offered by some of our recent results. The elastase-antileukoprotease complexes are rapidly dissociated when mixed with serum in vitro, although the equilibrium dissociation constant Ki of the complex is 1.2 X 10(-11) M. Furthermore, in a pure in vitro system, alpha 1-antitrypsin is able to dissociate a leukocyte elastase-antileukoprotease complex with the rate constant of 1.3 X 10(-4) X S-1. A small part of the antileukoprotease released from the elastase-antileukoprotease complex on mixture with serum is recovered bound by elastase-alpha 2-macroglobulin complexes. Antileukoprotease inhibits the enzymatic activity of elastase-alpha 2-macroglobulin complex relatively slowly. 1:1 elastase-alpha 2-macroglobulin complexes are, however, inhibited more readily than 2:1 saturated complexes.
D001991:Bronchitis / Q000201:enzymology*; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood*; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D013183:Sputum / Q000032:analysis*; D000511:alpha-Macroglobulins / Q000378:metabolism
D011480:Protease Inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D000511:alpha-Macroglobulins; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase