ArticleThe Journal of biological chemistry2012
Mast cell restricted mouse and human tryptase·heparin complexes hinder thrombin-induced coagulation of plasma and the generation of fibrin by proteolytically destroying fibrinogen.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Fecal microbiota transplantation reduces inflammation and modulates gene expression in HIV-infected double humanized-BLT (dHu-BLT) mice on antiretroviral therapy.Frontiers in immunology · 2026Article
- Hypofibrinogenemia Following an Anaphylactic Shock Caused by a Neuromuscular Blocking Agent-Case Report.Case reports in critical care · 2025Article
- Molecular convergence of risk variants for congenital heart defects leveraging a regulatory map of the human fetal heart.medRxiv : the preprint server for health sciences · 2024Article
- Involvement of Mast Cells in the Pathology of COVID-19: Clinical and Laboratory Parallels.Cells · 2024Article
- Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 mMolecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Predictive Factors Associated with Chronic Neck Pain in Patients with Cervical Degenerative Disease: A Retrospective Cohort Study.Journal of pain research · 2023Article
- Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis.Biomedicines · 2022Review
- Effects of Primary Mast Cell Disease on Hemostasis and Erythropoiesis.International journal of molecular sciences · 2021Review
- Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates fibrin-dependent plasmin generation on thrombin-activated platelets.Journal of thrombosis and haemostasis : JTH · 2020Article
- Dengue virus-elicited tryptase induces endothelial permeability and shock.The Journal of clinical investigation · 2019Article
- Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug.Toxicology letters · 2018Article
- Diffuse cutaneous mastocytosis with novel somatic KIT mutation K509I and association with tuberous sclerosis.Clinical case reports · 2018Article
- Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers.Journal of asthma and allergy · 2018Review
- Mast cell glycosaminoglycans.Glycoconjugate journal · 2017Review
- Experimental Arthritis Is Dependent on Mouse Mast Cell Protease-5.The Journal of biological chemistry · 2017Article
- The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis.Frontiers in immunology · 2017Review
- Proteome analysis of mast cell releasates reveals a role for chymase in the regulation of coagulation factor XIIIA levels via proteolytic degradation.The Journal of allergy and clinical immunology · 2017Article
- Elucidating novel disease mechanisms in severe asthma.Clinical & translational immunology · 2016Review
- Article
- Mast cells mediate malignant pleural effusion formation.The Journal of clinical investigation · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The mouse and human TPSB2 and TPSAB1 genes encode tetramer-forming tryptases stored in the secretory granules of mast cells (MCs) ionically bound to heparin-containing serglycin proteoglycans. In mice these genes encode mouse MC protease-6 (mMCP-6) and mMCP-7. The corresponding human genes encode a family of serine proteases that collectively are called hTryptase-β. We previously showed that the α chain of fibrinogen is a preferred substrate of mMCP-7. We now show that this plasma protein also is highly susceptible to degradation by hTryptase-β· and mMCP-6·heparin complexes and that Lys(575) is a preferred cleavage site in the protein α chain. Because cutaneous mouse MCs store substantial amounts of mMCP-6·heparin complexes in their secretory granules, the passive cutaneous anaphylaxis reaction was induced in the skin of mMCP-6(+)/mMCP-7(-) and mMCP-6(-)/mMCP-7(-) C57BL/6 mice. In support of the in vitro data, fibrin deposits were markedly increased in the skin of the double-deficient mice 6 h after IgE-sensitized animals were given the relevant antigen. Fibrinogen is a major constituent of the edema fluid that accumulates in tissues when MCs degranulate. Our discovery that mouse and human tetramer-forming tryptases destroy fibrinogen before this circulating protein can be converted to fibrin changes the paradigm of how MCs hinder fibrin deposition and blood coagulation internally. Because of the adverse consequences of fibrin deposits in tissues, our data explain why mice and humans lack a circulating protease inhibitor that rapidly inactivates MC tryptases and why mammals have two genes that encode tetramer-forming serine proteases that preferentially degrade fibrinogen.
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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.