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Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated platelets.
O A Hamad1, K N Ekdahl, P H Nilsson
1Rudbeck Laboratory C5, Division of Clinical Immunology, Uppsala University, Uppsala, Sweden.
Journal of Thrombosis and Haemostasis : JTH
|May 28, 2008
Summary
Platelets release chondroitin sulfate (CS) to activate the complement system, generating inflammatory signals. This discovery highlights a novel pathway for platelet-mediated inflammation.
Area of Science:
- Immunology
- Hematology
- Biochemistry
Background:
- Chondroitin sulfate (CS) is a glycosaminoglycan released by activated platelets.
- Platelet activation is implicated in various inflammatory processes.
Purpose of the Study:
- To investigate the hypothesis that platelet-derived CS can initiate fluid-phase complement activation.
- To identify the mechanisms and consequences of CS-mediated complement activation.
Main Methods:
- Platelet activation using Thrombin receptor-activating peptide (TRAP)-6 in plasma and whole blood.
- Measurement of complement activation products (C3a, sC5b-9).
- Enzymatic treatment with chondroitinase ABC and use of complement inhibitors (compstatin, C5aR antagonist).
- Identification of C1q as the CS recognition molecule.
Main Results:
- TRAP-6 induced fluid-phase complement activation, evidenced by C3a and sC5b-9 generation.
- Platelet-derived CS was confirmed as the initiator of complement activation.
- C1q directly bound to CS, initiating the complement cascade.
- CS-triggered complement activation led to increased leukocyte activation (CD11b expression) and leukocyte-platelet complex formation, mediated by C5a signaling.
Conclusions:
- Platelets release chondroitin sulfate (CS) to trigger fluid-phase complement activation.
- This pathway generates inflammatory signals via C5a, contributing to leukocyte activation and complex formation.
- CS represents a novel link between platelet activation and the inflammatory complement cascade.
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