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Streptokinase binds to lactate dehydrogenase subunit-M, which shares an epitope with plasminogen
1Department of Laboratory Medicine, Georgetown University Hospital, Washington, DC 20007.
Abstract:
The bacterial thrombolytic agent streptokinase binds to human, porcine, and chicken lactate dehydrogenase (EC 1.1.1.27; LD) isoenzyme subunit M, but not to the H or C subunits. There is amino acid sequence homology between LD and the streptokinase binding site on plasminogen to account for this interaction that results in the formation of high-molecular-mass complexes in serum that contain LD activity. Binding of highly immunogenic streptokinase with LD may lead to induction of anti-LD autoantibodies, known to occur in some patients after therapeutic administration of streptokinase for treatment of acute myocardial infarction. This interaction may also be a general mechanism for inducing autoimmunity against other proteins that share the streptokinase binding epitope.
Insights
The bacterial protein streptokinase binds to lactate dehydrogenase (LD) M subunits, potentially causing the immune system to produce anti-LD autoantibodies. This interaction may explain autoimmune responses seen after streptokinase therapy.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Streptokinase is a bacterial protein used as a thrombolytic agent.
- Lactate dehydrogenase (LD) is an enzyme with multiple isoenzyme subunits (M, H, C).
- Autoimmune responses can occur following therapeutic streptokinase administration.
Purpose of the Study:
- To investigate the interaction between streptokinase and lactate dehydrogenase (LD) isoenzymes.
- To explore the potential for streptokinase-LD binding to induce autoimmune reactions.
Main Methods:
- Analysis of amino acid sequence homology between LD and streptokinase binding sites.
- Observation of high-molecular-mass complex formation in serum containing LD activity.
Main Results:
- Streptokinase specifically binds to the M subunit of human, porcine, and chicken lactate dehydrogenase.
- No binding was observed with H or C subunits of LD.
- Amino acid sequence homology explains the interaction between streptokinase and LD.
- Formation of serum complexes containing LD activity was observed.
Conclusions:
- Streptokinase binding to LD M subunits may induce anti-LD autoantibodies.
- This interaction offers a potential mechanism for streptokinase-induced autoimmunity.
- The findings suggest a general mechanism for inducing autoimmunity against proteins sharing the streptokinase binding epitope.