Characterization of a macrophage-derived plasminogen-activator inhibitor. Similarities with placental urokinase inhibitor.
Human and mouse macrophages release a fibrinolytic inhibitor after stimulation by endotoxin in vitro. The released mouse inhibitor was indistinguishable in size by molecular-sieve chromatography from an intracellular form (approx. 50 kDa), and both inhibitors blocked urokinase directly as judged by a 125I-plasminogen conversion assay. The intracellular inhibitor was found mostly to dissociate from 125I-urokinase during sodium dodecyl sulphate/polyacrylamide-gel electrophoresis under reduced conditions, but a dodecyl sulphate-stable complex at 65-67 kDa was observed. Because of similarities in the reported size, stability and urokinase-binding properties of a placental urokinase inhibitor, the kinetic properties of the two inhibitors were compared. Under the reaction conditions employed (37 degrees C at pH7.4 in the presence of 0.2% Triton X-100), the association rate constants and equilibrium dissociation constants of the two inhibitors were indistinguishable, 3 X 10(5) M-1 X s-1 and 4 X 10(-10) M respectively. These data show that peritoneal macrophages contain a plasminogen-activator very similar to a previously recognized placental inhibitor. Although the inhibitor appears to be a trace protein in macrophages, placental macrophages may account for the accumulation of the inhibitor in placental tissue.
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D000818:Animals; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008809:Mice, Inbred C3H; D010920:Placenta / Q000201:enzymology; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D011247:Pregnancy; D013050:Spectrometry, Fluorescence; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator