Minor Role of Plasminogen in Complement Activation on Cell Surfaces
Satu Hyvärinen1, T Sakari Jokiranta1
1Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
Plos One
|December 5, 2015
Summary
Plasminogen deficiency may contribute to atypical hemolytic uremic syndrome (aHUS) not by regulating complement, but by impairing clot breakdown. This suggests non-complement factors are key in aHUS.
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- Atypical hemolytic uremic syndrome (aHUS) is a severe thrombotic microangiopathy often caused by complement gene mutations.
- Plasminogen deficiency has been observed in some aHUS patients, suggesting a potential link to complement regulation.
Purpose of the Study:
- To investigate the role of plasminogen in regulating complement activation in aHUS.
- To explore the potential of plasminogen and its active form, plasmin, in preventing complement-mediated damage to cells and in regulating platelet aggregation.
Main Methods:
- Hemolytic assays were used to assess complement activation.
- Flow cytometry was employed to measure complement activation product deposition on endothelial cells and platelets.
- Platelet aggregation assays were conducted in serum.
Main Results:
- Exogenously activated plasminogen (plasmin) inhibited complement activation at high concentrations, but zymogen plasminogen did not.
- Plasminogen did not restrict complement deposition on endothelial cells and showed only a weak, likely insignificant, effect on platelets.
- Plasminogen significantly hindered platelet aggregation by causing disintegration of formed platelet aggregates.
Conclusions:
- Plasminogen is not a significant regulator of complement on self-cells in the context of aHUS.
- Reduced plasmin's proteolytic activity on thrombi, rather than complement dysregulation, may explain plasminogen deficiency's association with aHUS.
- These findings highlight the importance of non-complement factors in aHUS pathogenesis.
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