ArticleBlood2011
The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217A.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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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
25 citing papers in PubMed, 38 citations in OpenAlex.
- Trial
- Prothrombin prevents fatal T cell-dependent anemia during chronic virus infection of mice.JCI insight · 2025Article
- Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial.Communications medicine · 2024Article
- Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis.American journal of physiology. Cell physiology · 2024Article
- Thrombin generation and activity in multiple sclerosis.Metabolic brain disease · 2021Review
- Host fibrinogen drives antimicrobial function inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Role of the coagulation system in the pathogenesis of sickle cell disease.Blood advances · 2019Article
- Coagulopathies and inflammatory diseases: '…glimpse of a Snark'.Current opinion in immunology · 2018Review
- The non-haemostatic role of platelets in systemic lupus erythematosus.Nature reviews. Rheumatology · 2018Review
- Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Detection of Subclinical Arthritis in Mice by a Thrombin Receptor-Derived Imaging Agent.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Intra-Articular Injections of Autologous Conditioned Serum to Treat Pain from Meniscal Lesions.Sports medicine international open · 2017Article
- Urokinase plasminogen activator and receptor promote collagen-induced arthritis through expression in hematopoietic cells.Blood advances · 2017Article
- Structural Architecture of Prothrombin in Solution Revealed by Single Molecule Spectroscopy.The Journal of biological chemistry · 2016Article
- Article
- Article
- Thrombin mutant W215A/E217A treatment improves neurological outcome and attenuates central nervous system damage in experimental autoimmune encephalomyelitis.Metabolic brain disease · 2015Article
- Coagulation takes center stage in inflammation.Blood · 2015Article
- WEDGE: an anticoagulant thrombin mutant produced by autoactivation.Journal of thrombosis and haemostasis : JTH · 2015Article
- Plasminogen is a joint-specific positive or negative determinant of arthritis pathogenesis in mice.Arthritis & rheumatology (Hoboken, N.J.) · 2014Article
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Thrombin is a positive mediator of thrombus formation through the proteolytic activation of protease-activated receptors (PARs), fibrinogen, factor XI (fXI), and other substrates, and a negative regulator through activation of protein C, a natural anticoagulant with anti-inflammatory/cytoprotective properties. Protease-engineering studies have established that 2 active-site substitutions, W215A and E217A (fII(WE)), result in dramatically reduced catalytic efficiency with procoagulant substrates while largely preserving thrombomodulin (TM)-dependent protein C activation. To explore the hypothesis that a prothrombin variant favoring antithrombotic pathways would be compatible with development but limit inflammatory processes in vivo, we generated mice carrying the fII(WE) mutations within the endogenous prothrombin gene. Unlike fII-null embryos, fII(WE/WE) mice uniformly developed to term. Nevertheless, these mice ultimately succumbed to spontaneous bleeding events shortly after birth. Heterozygous fII(WT/WE) mice were viable and fertile despite a shift toward an antithrombotic phenotype exemplified by prolonged tail-bleeding times and times-to-occlusion after FeCl₃ vessel injury. More interestingly, prothrombin(WE) expression significantly ameliorated the development of inflammatory joint disease in mice challenged with collagen-induced arthritis (CIA). The administration of active recombinant thrombin(WE) also suppressed the development of CIA in wild-type mice. These studies provide a proof-of-principle that pro/thrombin variants engineered with altered substrate specificity may offer therapeutic opportunities for limiting inflammatory disease processes.
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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.