Related Experiment Videos
U937 cells can utilize plasminogen activator to regulate human interferon-gamma
M J Parmely1, K E Sterner, A Gale
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66160-7420.
Journal of Interferon Research
|December 1, 1993
Summary
Urokinase-type plasminogen activator (uPA) produced by U937 cells inactivates interferon-gamma (IFN-gamma) via plasmin. This suggests mononuclear phagocytes can regulate cytokine activity.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Urokinase-type plasminogen activator (uPA) is crucial for cell migration and tissue remodeling.
- Interferon-gamma (IFN-gamma) is a key cytokine involved in immune responses.
Purpose of the Study:
- To investigate the role of uPA produced by U937 cells in the inactivation of recombinant interferon-gamma (rIFN-gamma).
- To explore the mechanism of rIFN-gamma inactivation by U937 cells and its regulation.
Main Methods:
- Culturing U937 promonocytic cells and blood monocytes in serum-free conditions with plasminogen.
- Assessing plasmin activity and rIFN-gamma antiviral activity.
- Utilizing inhibitors of uPA and plasmin.
- Analyzing rIFN-gamma electrophoretic mobility.
- Evaluating the induction of Fc receptors by rIFN-gamma.
Main Results:
- U937 cells produced plasmin in the presence of plasminogen, leading to the destruction of rIFN-gamma antiviral activity.
- rIFN-gamma inactivation was mediated by plasmin and prevented by uPA and plasmin inhibitors.
- Cultured U937 cells and monocytes showed increased surface uPA, plasmin production, and rIFN-gamma inactivation.
- Exogenous plasminogen inhibited rIFN-gamma's ability to induce Fc receptors on U937 cells.
Conclusions:
- Mononuclear phagocytes, through uPA, can regulate cytokine activity in vitro.
- U937 cells control their own activation by inactivating rIFN-gamma via uPA-mediated plasmin generation.
- These findings highlight a novel mechanism for cytokine regulation by immune cells.