The Functional Roles and the Potential as Drug Targets of Glycoproteins Regulating Complement and Coagulation Pathways
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- Mizuno Tomohiro
- Department of Clinical Pharmacy, School of Medicine, Fujita Health University
Bibliographic Information
- Other Title
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- 播種性血管内凝固症候群における補体–凝固系を制御する糖鎖タンパクの機能的役割と創薬ターゲットとしての可能性
Abstract
<p>Complement (C) activation occurs via three pathways, namely the classical, lectin, and alternative pathways. Intercommunication occurs between the complement and coagulation systems, which can trigger tissue injury and inflammation. Disseminated intravascular coagulation (DIC) is a life-threatening disease characterized by disordered coagulation and systemic inflammation; here, the intercommunication between the complement and coagulation systems contributes to the development of DIC. Extracellular histones, which are contributors to the damage-associated molecular pattern, induce severe thrombosis. C5 is a key molecule in the intercommunication between the complement and coagulation systems and is associated with the development of lethal histone-induced thrombosis. Heparin and chondroitin sulfate (CS) are negatively charged, allowing them to bind to extracellular histones. As the coagulation system is less affected by CS than heparin, CS shows potential as an effective drug for the treatment of patients with DIC who have a high risk of bleeding. Complement receptor type-1-related gene Y (Crry) inhibits the complement pathway via binding to C3b and C4b. Hence, Crry is a potent inhibitor of the classical and alternative C pathways. The expression of Crry is decreased by the endothelial damage induced by extracellular histones. Crry dysfunction promotes the activation of C on the surface of endothelial cells. The prevention of C3 cleavage on endothelial cells might be a useful therapy targeting acute lung injury.</p>
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 143 (9), 707-712, 2023-09-01
The Pharmaceutical Society of Japan
