Limited proteolysis by macrophage elastase inactivates human alpha 1-proteinase inhibitor.
Inflammatory mouse peritoneal macrophages secrete a metalloproteinase that is not inhibited by alpha 1-proteinase inhibitor. This proteinase, macrophage elastase, recognizes alpha 1-proteinase inhibitor with macrophage elastase does not involve a stable proteinase-inhibitor complex and results in the proteolytic removal of a peptide of apparent molecular weight 4,000-5,000 from the inhibitor. After degradation by macrophage elastase, alpha 1-proteinase inhibitor is no longer able to inhibit human granulocyte elastase, a serine proteinase implicated in the pathogenesis of emphysema. Macrophage elastase apparently does not degrade human granulocyte elastase-alpha 1-proteinase inhibitor complexes or release active granulocyte elastase from these complexes. The ability of macrophage elastase to degrade alpha 1-proteinase inhibitor is inhibited by EDTA and alpha 2-macroglobulin.
D006098:Granulocytes / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D008264:Macrophages / Q000201:enzymology*; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase