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Updated: Jul 13, 2026
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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
High molecular weight kininogen binds to unstimulated platelets
The Journal of Clinical Investigation
|July 1, 1986
Summary
Unstimulated platelets bind high molecular weight kininogen (HMWK) via a specific zinc-dependent site on their external membrane. This interaction may influence contact phase activation pathways.
Area of Science:
- Biochemistry
- Hematology
- Cell Biology
Background:
- High molecular weight kininogen (HMWK) plays a role in contact phase activation.
- The interaction of HMWK with unstimulated platelets is not fully understood.
Purpose of the Study:
- To investigate the presence and characteristics of HMWK binding sites on unstimulated platelet membranes.
- To determine the role of divalent cations in HMWK-platelet binding.
Main Methods:
- Radioligand binding assays using 125I-HMWK.
- Competition assays with excess HMWK and other proteins.
- Divalent cation dependency studies (Zn++, Mg++, Ca++).
Main Results:
- 125I-HMWK specifically bound to unstimulated platelets in a zinc-dependent manner.
- Binding was maximal at 50 microM Zn++ and not supported by Mg++ or Ca++.
- HMWK competed with 125I-HMWK for binding, while other proteins did not.
- A single class of high-affinity, saturable binding sites for HMWK was identified (Kd ≈ 0.99 nM, 3,313 sites/platelet).
Conclusions:
- Unstimulated platelets possess specific, high-affinity binding sites for HMWK on their external membrane.
- Zinc is essential for this binding interaction.
- These findings suggest a potential role for platelet-bound HMWK in modulating contact phase activation.
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