ArticleBlood2016
Polyphosphate is a novel cofactor for regulation of complement by a serpin, C1 inhibitor.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Inhibition of IP6K1 suppresses NPA formation via platelet short-chain polyphosphate polymers in necrotizing enterocolitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Research progress on serine proteases in the field of male reproduction: a narrative review.Translational andrology and urology · 2026Review
- Integrated Analysis of Bulk RNA Sequencing, eQTL, GWAS, and Single-Cell RNA Sequencing Reveals Key Genes in Hepatocellular Carcinoma.Journal of cellular and molecular medicine · 2025Article
- Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway.Cancers · 2024Article
- The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.International journal of molecular sciences · 2024Review
- Polyphosphate-loaded silk fibroin membrane as hemostatic agent in oral surgery: a pilot study.International journal of implant dentistry · 2023Article
- Bioenergetics of the polyphosphates accumulation inHeliyon · 2023Article
- Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro.International journal of molecular sciences · 2022Article
- Novel interaction of properdin and coagulation factor XI: Crosstalk between complement and coagulation.Research and practice in thrombosis and haemostasis · 2022Article
- Inorganic Polymeric Materials for Injured Tissue Repair: Biocatalytic Formation and Exploitation.Biomedicines · 2022Review
- Biomimetic Polyphosphate Materials: Toward Application in Regenerative Medicine.Progress in molecular and subcellular biology · 2022Article
- Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis.Frontiers in cardiovascular medicine · 2022Review
- Coagulation and complement: Key innate defense participants in a seamless web.Frontiers in immunology · 2022Review
- Bacterial polyphosphates induce CXCL4 and synergize with complement anaphylatoxin C5a in lung injury.Frontiers in immunology · 2022Article
- Proteome and functional decline as platelets age in the circulation.Journal of thrombosis and haemostasis : JTH · 2021Article
- Identification of the factor XII contact activation site enables sensitive coagulation diagnostics.Nature communications · 2021Article
- The role of complement in brain injury following intracerebral hemorrhage: A review.Experimental neurology · 2021Review
- Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate.Blood · 2021Article
- Therapeutic SERPINs: Improving on Nature.Frontiers in cardiovascular medicine · 2021Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The complement system plays a key role in innate immunity, inflammation, and coagulation. The system is delicately balanced by negative regulatory mechanisms that modulate the host response to pathogen invasion and injury. The serpin, C1-esterase inhibitor (C1-INH), is the only known plasma inhibitor of C1s, the initiating serine protease of the classical pathway of complement. Like other serpin-protease partners, C1-INH interaction with C1s is accelerated by polyanions such as heparin. Polyphosphate (polyP) is a naturally occurring polyanion with effects on coagulation and complement. We recently found that polyP binds to C1-INH, prompting us to consider whether polyP acts as a cofactor for C1-INH interactions with its target proteases. We show that polyP dampens C1s-mediated activation of the classical pathway in a polymer length- and concentration-dependent manner by accelerating C1-INH neutralization of C1s cleavage of C4 and C2. PolyP significantly increases the rate of interaction between C1s and C1-INH, to an extent comparable to heparin, with an exosite on the serine protease domain of the enzyme playing a major role in this interaction. In a serum-based cell culture system, polyP significantly suppressed C4d deposition on endothelial cells, generated via the classical and lectin pathways. Moreover, polyP and C1-INH colocalize in activated platelets, suggesting that their interactions are physiologically relevant. In summary, like heparin, polyP is a naturally occurring cofactor for the C1s:C1-INH interaction and thus an important regulator of complement activation. The findings may provide novel insights into mechanisms underlying inflammatory diseases and the development of new therapies.
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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.