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...

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Bibliographic Details
Published in:Biochemical journal 1985-08, Vol.230 (1), p.109-116
Main Authors: Chapman, Jr, H A, Stone, O L
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
electrophoresis
Electrophoresis, Polyacrylamide Gel
Female
Fibrinolysin - metabolism
Glycoproteins - metabolism
Humans
Kinetics
macrophages
Macrophages - enzymology
man
Mice
Mice, Inbred C3H
Placenta - enzymology
Plasminogen - metabolism
plasminogen activator
Plasminogen Activators - antagonists & inhibitors
Plasminogen Inactivators
Pregnancy
Spectrometry, Fluorescence
Urokinase-Type Plasminogen Activator - antagonists & inhibitors
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Summary: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.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj2300109