Abstract
Macrophages in the tissues have been shown to express receptor for urokinase-type plasminogen activator (uPAR) on their cell surface which plays an important role in cell invasion and attachment. We examined the effects of inflammatory mediators on the expression of uPAR employing U937 cells which have monocyte/ macrophage-like characteristics. U937 cells were incubated with various mediators such as interleukins (IL), tumor necrosis factors (TNF), dexamethasone, thrombin, fibrin fragment D, bradykinin, complement C5a, and components of the extracellular matrix. The uPAR expression on the cell surface was then analyzed by radio-ligand binding assay using125I-scuPA. The strongest enhancement of uPAR was observed in the cells stimulated by TNFα and TNFβ. IL-1β, IL-6, and C5a also increased the uPA binding sites with various patterns of affinity change. Dexamethasone decreased the uPA binding sites without changing the affinity. Fibrin fragment D and IL-3 reduced the affinity without changing the number of receptors. These findings suggest that the expression of uPAR in inflammatory cells could be modulated by various inflammatory mediators.
Similar content being viewed by others
References
Danø, K., A. Andreasen, J. Grøndahl-Hansen, P. Kristensen, L. S. Nielsen, andL. Skriver. 1985. Plasminogen activators, tissue degradation and cancer.Adv. Cancer Res. 44:139–266.
Ellis, V., N. Behrendt, andK. Danø. 1991. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor.J. Biol. Chem. 266:12752–12758.
Ellis, V., C. Pyke, J. Eriksen, H. Solberg, andK. Danø. 1992. The urokinase receptor: Involvement in cell surface proteolysis and cancer invasion.Ann. N.Y. Acad. Sci.667:13–31.
Schäfer, B. M., K. Maier, U. Eickhoff, R. F. Todd, andM. D. Kramer. 1994. Plasminogen activation in healing human wounds.Am. J. Pathol. 144:1269–1280.
Kirchheimer, J. C., Y-H. Nong, andH. G. Remold. 1988. IFN-γ, tumor necrosis factor-α, and urokinase regulate the expression of urokinase receptors on human monocytes.J. Immunol. 141:4229–4234.
PicoNE, R., E. L. Kajtaniak, L. S. Nielsen, N. Behrendt, M. R. Mastronicola, M. V. Cubellis, M. P. Stoppelli, S. Pedersen, K. Danø, andF. Blasi. 1989. Regulation of Urokinase receptors in monocytelike U937 cells by phorbol ester myristate acetate.J. Cell Biol. 108:693–702.
Reuning, U., andN. U. Bang. 1992. Regulation of the urokinase-type plasminogen activator receptor on vascular smooth muscle cells is under the control of thrombin and other mitogens.Arterioscler. Thromb. 12:1161–1170.
Nielsen, L. S., G. M. Kellerman, N. Behrendt, R. Picone, K. Danø, andF. Blasi. 1988. A 55,000–60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification.J. Biol. Chem. 263:2358–2363.
Conese, M., andF. Blasi. 1995. Urokinase/urokinase receptor system: Internalization/degradation of urokinase-serpin complexes: Mechanism and regulation.Biol. Chem. Hoppe-Seyler. 376:143–155.
Paulsson, M. 1992. Basement membrane proteins: Structure, assembly, and cellular interactions.Crit. Rev. Biochem. Mol. Biol. 27:93–127.
Pyke, C., P. Kristensen, E. Ralfkiaer, J. Grøndahl-Hansen, J. Eriksen, F. Blasi, andK. Danø. 1991. Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas.Am. J. Pathol. 138:1059–1067.
Behrendt, N., E. Rønne, M. Ploug, T. Petri, D. Løber, L. S. Nielsen, W-D. Schleuning, F. Blasi, E. Appella, andK. Danø. 1990. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants.J. Biol. Chem. 265:6453–6460.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yoshida, E., Tsuchiya, K., Sugiki, M. et al. Modulation of the receptor for urokinase-type plasminogen activator in macrophage-like U937 cells by inflammatory mediators. Inflammation 20, 319–326 (1996). https://doi.org/10.1007/BF01488206
Issue Date:
DOI: https://doi.org/10.1007/BF01488206