ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Cross-Talk between the Complement Pathway and the Contact Activation System of Coagulation: Activated Factor XI Neutralizes Complement Factor H.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial.Frontiers in immunology · 2023Trial
- Complement Factor H as a Novel Predictive Biomarker for Deep Vein Thrombosis Recurrence: A Prospective Cohort Study.Journal of thrombosis and thrombolysis · 2026Article
- Antibodies to mannose-binding lectin and factor XI Inhibit Shiga toxin-induced kidney injury additively in a murine model.Pediatric research · 2026Article
- Bacterial infection and activation of the contact pathway of coagulation.Blood vessels, thrombosis & hemostasis · 2025Review
- Protective effects of factor XI inhibition by abelacimab in a baboon model of live Staphylococcus aureus sepsis.Journal of thrombosis and haemostasis : JTH · 2025Article
- Review
- [Berberine ameliorates coronary artery endothelial cell injury in Kawasaki disease through complement and coagulation cascades].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- Hemostasis and complement in allogeneic hematopoietic stem cell transplantation: clinical significance of two interactive systems.Bone marrow transplantation · 2024Review
- Complement factor H in molecular regulation of angiogenesis.Medical review (2021) · 2024Review
- Factor XII promotes the thromboinflammatory response in a rat model of venoarterial extracorporeal membrane oxygenation.The Journal of thoracic and cardiovascular surgery · 2024Article
- Biology of factor XI.Blood · 2024Review
- Serum Biomarkers of Vascular Involvement in Childhood Uveitis.Translational vision science & technology · 2024Article
- Coagulation and platelet biology at the intersection of health and disease: illustrated capsules of the 11th Symposium on Hemostasis at the University of North Carolina.Research and practice in thrombosis and haemostasis · 2024Article
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots.Frontiers in immunology · 2024Article
- Activation of coagulation FXI promotes endothelial inflammation and amplifies platelet activation in a nonhuman primate model of hyperlipidemia.Research and practice in thrombosis and haemostasis · 2024Article
- The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome.Biomolecules · 2023Review
- Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis.JAMA ophthalmology · 2023Article
- Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression.Molecular immunology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Complement factor H (CFH) is the major inhibitor of the alternative pathway of the complement system and is structurally related to beta2-glycoprotein I, which itself is known to bind to ligands, including coagulation factor XI (FXI). We observed reduced complement activation when FXI activation was inhibited in a baboon model of lethal systemic inflammation, suggesting cross-talk between FXI and the complement cascade. It is unknown whether FXI or its activated form, activated FXI (FXIa), directly interacts with the complement system. We explored whether FXI could interact with and inhibit the activity of CFH. We found that FXIa neutralized CFH by cleavage of the R341/R342 bonds. FXIa reduced the capacity of CFH to enhance the cleavage of C3b by factor I and the decay of C3bBb. The binding of CFH to human endothelial cells was also reduced after incubating CFH with FXIa. The addition of either short- or long-chain polyphosphate enhanced the capacity of FXIa to cleave CFH. FXIa also cleaved CFH that was present on endothelial cells and in the secretome from blood platelets. The generation of FXIa in plasma induced the cleavage of CFH. Moreover, FXIa reduced the cleavage of C3b by factor I in serum. Conversely, we observed that CFH inhibited FXI activation by either thrombin or FXIIa. Our study provides, to our knowledge, a novel molecular link between the contact pathway of coagulation and the complement system. These results suggest that FXIa generation enhances the activity of the complement system and thus may potentiate the immune response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.