Concomitant secretion of prourokinase and of a plasminogen activator- specific inhibitor by cultured human monocytes-macrophages

doi:10.1084/jem.159.6.1653

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Concomitant secretion of prourokinase and of a plasminogen activator- specific inhibitor by cultured human monocytes-macrophages

JD Vassalli, JM Dayer, A Wohlwend and D Belin

The plasminogen activator (PA) produced by freshly purified human monocytes-macrophages and histiocytic, lymphoma-derived U 937 cells was analyzed by zymography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and found to migrate with an apparent Mr of 55,000, identical to that of urokinase (Uk). By immunoprecipitation with antibodies specific for the two different types of PA, the enzyme was shown to be immunologically related to urokinase, and not to tissue PA. Urokinase was secreted in the form of the inactive Mr 55,000 zymogen prourokinase , and could be converted to the active Mr 55,000 enzyme by limited proteolysis with plasmin. Conditioned media from cultures of U 937 cells and monocytes-macrophages inhibited the fibrinolytic activity of exogenously added urokinase. Using [125I]- labeled urokinase we observed the formation of an enzyme-ligand complex, which was not dissociated by boiling in SDS and migrated with an apparent Mr 40,000 daltons higher than the free enzyme; since complexed urokinase was functionally inactivated as a PA, the ligand is an inhibitor of urokinase. This inhibitor is different from fibroblast- produced protease- nexin , in that it did not interact with thrombin. These results suggest that plasminogen activation by mononuclear phagocytes can be modulated through the secretion of both (pro)enzyme and a specific inhibitor.
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FABBRINI, M. S., CARPANI, D., SORIA, M. R., CERIOTTI, A. (2000). Cytosolic immunization allows the expression of preATF-saporin chimeric toxin in eukaryotic cells. FASEB J. 14: 391-398 [Abstract] [Full Text]
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Ny, A., Leonardsson, G., Hägglund, A.-C., Hägglöf, P., Ploplis, V. A., Carmeliet, P., Ny, T. (1999). Ovulation in Plasminogen-Deficient Mice. Endocrinology 140: 5030-5035 [Abstract] [Full Text]
Schwartz, B. S., Espana, F. (1999). Two Distinct Urokinase-Serpin Interactions Regulate the Initiation of Cell Surface-associated Plasminogen Activation. J. Biol. Chem. 274: 15278-15283 [Abstract] [Full Text]
Barazzone, C., Donati, Y. R., Rochat, A. F., Vesin, C., Kan, C.-D., Pache, J. C., Piguet, P. F. (1999). Keratinocyte Growth Factor Protects Alveolar Epithelium and Endothelium from Oxygen-Induced Injury in Mice. Am. J. Pathol. 154: 1479-1487 [Abstract] [Full Text]
Olofsson, B., Korpelainen, E., Pepper, M. S., Mandriota, S. J., Aase, K., Kumar, V., Gunji, Y., Jeltsch, M. M., Shibuya, M., Alitalo, K., Eriksson, U. (1998). Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc. Natl. Acad. Sci. USA 95: 11709-11714 [Abstract] [Full Text]
Koyama, H., Reidy, M. A. (1998). Expression of Extracellular Matrix Proteins Accompanies Lesion Growth in a Model of Intimal Reinjury. Circ. Res. 82: 988-995 [Abstract] [Full Text]
Ploplis, V. A., French, E. L., Carmeliet, P., Collen, D., Plow, E. F. (1998). Plasminogen Deficiency Differentially Affects Recruitment of Inflammatory Cell Populations in Mice. Blood 91: 2005-2009 [Abstract] [Full Text]
Ginestra, A., Monea, S., Seghezzi, G., Dolo, V., Nagase, H., Mignatti, P., Vittorelli, M. L. (1997). Urokinase Plasminogen Activator and Gelatinases Are Associated with Membrane Vesicles Shed by Human HT1080 Fibrosarcoma Cells. J. Biol. Chem. 272: 17216-17222 [Abstract] [Full Text]
Sabapathy, K. T., Pepper, M. S., Kiefer, F., Mohle-Steinlein, U., Tacchini-Cottier, F., Fetka, I., Breier, G., Risau, W., Carmeliet, P., Montesano, R., Wagner, E. F. (1997). Polyoma Middle T-induced Vascular Tumor Formation: The Role of the Plasminogen Activator/Plasmin System. J. Cell Biol. 137: 953-963 [Abstract] [Full Text]
Tsirka, S. E., Rogove, A. D., Bugge, T. H., Degen, J. L., Strickland, S. (1997). An Extracellular Proteolytic Cascade Promotes Neuronal Degeneration in the Mouse Hippocampus. J. Neurosci. 17: 543-552 [Abstract] [Full Text]
Mandriota, S. J., Menoud, P.-A., Pepper, M. S. (1996). Transforming Growth Factor beta1 Down-regulates Vascular Endothelial Growth Factor Receptor 2/flk-1 Expression in Vascular Endothelial Cells. J. Biol. Chem. 271: 11500-11505 [Abstract] [Full Text]
Mikus, P., Ny, T. (1996). Intracellular Polymerization of the Serpin Plasminogen Activator Inhibitor Type 2. J. Biol. Chem. 271: 10048-10053 [Abstract] [Full Text]
Padro, T., Emeis, J. J., Steins, M., Schmid, K. W., Kienast, J. (1995). Quantification of Plasminogen Activators and Their Inhibitors in the Aortic Vessel Wall in Relation to the Presence and Severity of Atherosclerotic Disease. Arterioscler. Thromb. Vasc. Bio. 15: 893-902 [Abstract] [Full Text]
Mandriota, S. J., Seghezzi, G., Vassalli, J.-D., Ferrara, N., Wasi, S., Mazzieri, R., Mignatti, P., Pepper, M. S. (1995). Vascular Endothelial Growth Factor Increases Urokinase Receptor Expression in Vascular Endothelial Cells. J. Biol. Chem. 270: 9709-9716 [Abstract] [Full Text]
Naldini, L., Vigna, E., Bardelli, A., Follenzi, A., Galimi, F., Comoglio, P. M. (1995). Biological Activation of pro-HGF (Hepatocyte Growth Factor) by Urokinase Is Controlled by a Stoichiometric Reaction. J. Biol. Chem. 270: 603-611 [Abstract] [Full Text]
Carroll, P., Richards, W., Darrow, A., Wells, J., Strickland, S (1993). Preimplantation mouse embryos express a cell surface receptor for tissue-plasminogen activator. Development 119: 191-198 [Abstract]
Boulukos, K E, Pognonec, P, Sariban, E, Bailly, M, Lagrou, C, Ghysdael, J (1990). Rapid and transient expression of Ets2 in mature macrophages following stimulation with cMGF, LPS, and PKC activators.. Genes Dev. 4: 401-409 [Abstract]