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Inhibition of platelet function by recombinant soluble ecto-ADPase/CD39
R B Gayle1, C R Maliszewski, S D Gimpel
1Immunex Corporation, Seattle, Washington 98101, USA. gayler@immunex.com
The Journal of Clinical Investigation
|June 13, 1998
Summary
A novel soluble form of CD39, an enzyme that metabolizes platelet-activating molecules, was developed. This soluble CD39 effectively inhibits platelet aggregation and reactivity, showing potential as an antithrombotic therapy for cardiovascular diseases.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Pharmacology
Background:
- Platelet accumulation at vascular injury sites causes vessel occlusion, a significant challenge in cardiovascular medicine.
- Endothelial cell CD39 metabolizes ATP and ADP, crucial for inhibiting platelet recruitment.
Purpose of the Study:
- To design and characterize a recombinant soluble form of human CD39 as a novel antithrombotic agent.
- To evaluate the therapeutic potential of soluble CD39 in inhibiting platelet-mediated thrombosis.
Main Methods:
- Designed and isolated recombinant soluble human CD39 from transfected cell lines (COS-1 and CHO).
- Purified soluble CD39 using anti-CD39 immunoaffinity chromatography.
- Assessed ATPase and ADPase activities, inhibition of ADP- and collagen-induced platelet aggregation, and in vivo pharmacokinetics in mice.
Main Results:
- Purified soluble CD39 demonstrated significant ATPase and ADPase activities.
- Soluble CD39 effectively blocked ADP-induced platelet aggregation and inhibited collagen-induced platelet reactivity in vitro.
- Intravenously administered soluble CD39 exhibited a long half-life (nearly 2 days) in mice, indicating sustained activity.
Conclusions:
- Recombinant soluble CD39 is a potent inhibitor of platelet aggregation and reactivity.
- Soluble CD39 represents a promising therapeutic candidate for treating platelet-mediated thrombotic disorders.
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