Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo

Area of Science:

• Biochemistry
• Hematology
• Immunology

Background:

• Platelets are crucial in hemostasis, thrombosis, and inflammation.
• The molecular mechanisms linking platelets to these processes are under investigation.

Purpose of the Study:

• To investigate the role of inorganic polyphosphate (polyP) released by activated platelets.
• To determine polyP's involvement in thrombosis, inflammation, and coagulation.

Main Methods:

• Investigated polyP binding to factor XII and its activation.
• Assessed polyP's effect on bradykinin release and vascular permeability in mice.
• Studied the impact of factor XII, bradykinin receptors, and phosphatases on polyP-mediated effects.
• Examined polyP's role in plasma clotting and pulmonary embolism models.
• Analyzed polyP's effect in Hermansky-Pudlak Syndrome patient plasma.

Main Results:

• Activated platelets release polyP, which activates factor XII and triggers bradykinin release.
• PolyP increases vascular permeability and fluid extravasation, effects dependent on factor XII and bradykinin receptors.
• PolyP initiates plasma clotting via the contact pathway and causes lethal pulmonary embolism.
• Targeting polyP with phosphatases inhibits platelet procoagulant activity and thrombosis.
• PolyP addition corrects defective clotting in Hermansky-Pudlak Syndrome patient plasma.

Conclusions:

• Inorganic polyphosphate (polyP) is a novel mediator released by activated platelets.
• PolyP plays fundamental roles in platelet-driven inflammatory and procoagulant disorders.
• Targeting polyP presents a potential therapeutic strategy for thrombotic and inflammatory conditions.