A fast-acting elastase inhibitor in human monocytes.
A proteinase inhibitor active against neutrophil and pancreatic elastase was detected in extracts of cultured human monocytes and the human monocyte-like cell line U937. This component forms a covalent complex with the active site of elastase; the complex is stable in boiling sodium dodecyl sulfate solution, and is susceptible to nucleophilic cleavage. The activity of the elastase inhibitor is not detected in extracts of freshly isolated monocytes, but becomes detectable when the monocytes are allowed to mature in culture, with maximum levels occurring at 5-7 d. The monocyte inhibitor is fast-acting; its reaction with 125I-labeled elastase is complete in less than 1 min at 37 degrees C. Analysis by electrophoresis and studies using a heteroantiserum to alpha 1-proteinase inhibitor demonstrated that the elastase inhibitor of monocytes/U937 cells is not identical to alpha 1-proteinase inhibitor, the major elastase inhibitor of blood plasma. The extent of conversion of 125I-elastase to the 125I-elastase-inhibitor complex is proportional to the amount of U937 extract or cultured monocyte extract, indicating that this reaction can serve to quantify the elastase inhibitor. The elastase inhibitor is an abundant component in mature monocytes, with greater than or equal to 1.5 X 10(6) molecules/cell (greater than or equal to 12 micrograms per 10(8) cells, greater than 0.1% of total cell protein). Its mol wt is estimated at 50,000. Thus, the monocyte inhibitor should be classified as a putative regulator of neutrophil (and monocyte) elastase activity at inflammatory sites. This designation is based on the properties of the molecule, including its high concentration in maturing monocytes, its affinity for elastase, and its fast reaction with this enzyme.
D001798:Blood Proteins / Q000502:physiology; D002448:Cell Adhesion; D002460:Cell Line; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology* / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000502:physiology*; D015843:Serpins; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D015843:Serpins; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase