ArticleProceedings of the National Academy of Sciences of the United States of America2012
Impaired function of the Tie-2 receptor contributes to vascular leakage and lethality in anthrax.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 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
41 citing papers in PubMed, 54 citations in OpenAlex.
- Tie2 protects the vasculature against thrombus formation in systemic inflammation.The Journal of clinical investigation · 2018Trial
- Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria.Science translational medicine · 2016Trial
- Anthrax toxins exacerbate sepsis-induced coagulopathy and endothelial dysfunction in a baboon model of anthrax.Journal of thrombosis and haemostasis : JTH · 2026Article
- Deletion of the angiopoietin receptor Tie2 enhances proliferation and sprouting of cardiac endothelial cells.Angiogenesis · 2026Article
- Infectious bacteria as biological warfare agents: mechanisms, epidemiological threats, and defense strategies.Frontiers in bioengineering and biotechnology · 2026Review
- Endothelial barrier disorder in hereditary angioedema: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Cathepsin K cleavage of angiopoietin-2 creates detrimental Tie2 antagonist fragments in sepsis.The Journal of clinical investigation · 2025Article
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Molecular profiling of the stroke-induced alterations in the cerebral microvasculature reveals promising therapeutic candidates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mechanisms of immune effector cell-associated neurotoxicity syndrome after CAR-T treatment.WIREs mechanisms of disease · 2022Review
- New Insights into Clinical and Mechanistic Heterogeneity of the Acute Respiratory Distress Syndrome: Summary of the Aspen Lung Conference 2021.American journal of respiratory cell and molecular biology · 2022Article
- Flow-dependent regulation of endothelial Tie2 by GATA3 in vivo.Intensive care medicine experimental · 2021Article
- Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti-Thy-1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway.Cell proliferation · 2021Article
- The Angiopoietin-Tie2 Pathway in Critical Illness.Critical care clinics · 2020Review
- Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries.Frontiers in pediatrics · 2020Article
- Inhibiting Airway Smooth Muscle Contraction Using Pitavastatin: A Role for the Mevalonate Pathway in Regulating Cytoskeletal Proteins.Frontiers in pharmacology · 2020Article
- Article
- Molecular Regulation of Acute Tie2 Suppression in Sepsis.Critical care medicine · 2018Observational
- Matrix metalloproteinase inhibitors enhance the efficacy of frontline drugs against Mycobacterium tuberculosis.PLoS pathogens · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
The anthrax lethal toxin (LT) enters host cells and enzymatically cleaves MAPKKs or MEKs. How these molecular events lead to death from anthrax remains poorly understood, but published reports suggest a direct effect of LT on vascular permeability. We have found that LT challenge in mice disrupts signaling through Tie-2, a tonically activated receptor tyrosine kinase in the endothelium. Genetic manipulations favoring Tie-2 activation enhanced interendothelial junctional contacts, prevented vascular leakage, and promoted survival following a lethal dose of LT. Cleavage of MEK1/2 was necessary for LT to induce endothelial barrier dysfunction, and activated Tie-2 signaled through the uncleaved fraction of MEKs to prevent LT's effects on the endothelium. Finally, primates infected with toxin-secreting Bacillus anthracis bacilli developed a rapid and marked imbalance in the endogenous ligands that signal Tie-2, similar to that seen in LT-challenged mice. Our results show that B. anthracis LT blunts signaling through Tie-2, thereby weakening the vascular barrier and contributing to lethality of the disease. Measurement of circulating Tie-2 ligands and manipulation of Tie-2 activity may represent future prognostic and therapeutic avenues for humans exposed to B. anthracis.
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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.