Ceruloplasmin: plasma inhibitor of the oxidative inactivation of alpha 1-protease inhibitor.
When leukocyte lysosomal extracts are used as a source of elastase and are combined with a fraction of plasma containing sufficient alpha 1-protease inhibitor (alpha 1-Pi) to inhibit all but 30 to 40% of the elastase amidase activity, elastolysis occurs at 69% of the rate of the uninhibited elastase controls (0.125 M NaCl; pH, 6.5). Proteolysis of elastin requires the presence of NaCl. At pH 8.6, elastolysis is decreased to 30 to 40% of free elastase controls by 1.0 M NaCl. At pH 6.5, on the other hand, elastolysis is increased to 83% of the control values by these higher NaCl concentrations. The activity of human leukocyte myeloperoxidase is optimal at pH 6 to 6.5 and at NaCl concentrations between 0.25 and 1.0 M. Purified myeloperoxidase, alpha 1-Pi, and elastase, in the presence of NaCl and hydrogen peroxide, can reproduce this phenomenon at pH 6.5, suggesting that the occurrence of elastolysis in lysosomal extract-plasma mixtures may in part be a result of the oxidative inactivation of alpha 1-Pi by myeloperoxidase present in the lysosomal extract. Human ceruloplasmin, the major antioxidant of plasma, inhibits this myeloperoxidase-dependent reaction, without interfering either with free elastase activity or with the appearance of activity in plasma-lysosomal extract mixtures at pH 8.6. The "antioxidant" activity of ceruloplasmin is inhibited by azide. These results suggest that antioxidants such as ceruloplasmin may be an important determinant of lung defense in persons chronically exposed to oxidants.
D000975:Antioxidants; D001386:Azides / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D002570:Ceruloplasmin / Q000494:pharmacology*; D004549:Elastin / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007962:Leukocytes / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D019810:Sodium Azide; D012965:Sodium Chloride / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000975:Antioxidants; D001386:Azides; D001798:Blood Proteins; D000515:alpha 1-Antitrypsin; D012965:Sodium Chloride; D004549:Elastin; D019810:Sodium Azide; D009195:Peroxidase; D002570:Ceruloplasmin; D010196:Pancreatic Elastase