ArticleBlood2005
Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers.
Article in Blood, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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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
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.Intensive care medicine · 2020Guideline
- Interaction of Shiga toxin with the A-domains and multimers of von Willebrand Factor.The Journal of biological chemistry · 2013Trial
- Antibody Screening and Binding Prediction Analysis Targeting Stx2.Antibodies (Basel, Switzerland) · 2026Article
- Microfluidic Shear-Based Assay for Assessing ADAMTS13 Activity Under Flow.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Molecular determinants of STEC-HUS: from complement activation to microvascular thrombosis.Frontiers in immunology · 2026Article
- Neutrophils and NETs in kidney disease.Nature reviews. Nephrology · 2025Review
- Weibel-Palade bodies: function and role in thrombotic thrombocytopenic purpura and in diarrhea phase of STEC-hemolytic uremic syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Targeting neutrophil extracellular trap accumulation under flow in patients with immune-mediated thrombotic thrombocytopenic purpura.Blood advances · 2024Article
- The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome.Biomolecules · 2023Review
- Article
- Immune-mediated thrombotic thrombocytopenic purpura plasma induces calcium- and IgG-dependent endothelial activation: correlations with disease severity.Haematologica · 2023Article
- Endothelial dysfunction and immunothrombosis in sepsis.Frontiers in immunology · 2023Review
- Thrombotic microangiopathies: An illustrated review.Research and practice in thrombosis and haemostasis · 2022Review
- Complement Mediated Endothelial Damage in Thrombotic Microangiopathies.Frontiers in medicine · 2022Review
- Neutrophil Extracellular Traps Induced by Shiga Toxin and Lipopolysaccharide-Treated Platelets Exacerbate Endothelial Cell Damage.Frontiers in cellular and infection microbiology · 2022Article
- Predictive role of endothelial cell activation in cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukaemia.Journal of cellular and molecular medicine · 2021Article
- Phenotypic diversity and metabolic specialization of renal endothelial cells.Nature reviews. Nephrology · 2021Review
- The effects of sepsis on endothelium and clinical implications.Cardiovascular research · 2021Article
- The Glomerular Endothelium Restricts Albumin Filtration.Frontiers in medicine · 2021Review
- Cerebral sinovenous thrombosis in pediatric hemolytic uremic syndrome.Research and practice in thrombosis and haemostasis · 2020Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Shiga toxin 1 (Stx-1) and Stx-2 produced by enterohemorrhagic Escherichia coli cause the diarrhea-associated hemolytic uremic syndrome (HUS). This type of HUS is characterized by obstruction of the glomeruli and renal microvasculature by platelet-fibrin thrombi, acute renal failure, thrombocytopenia, microvascular hemolytic anemia, and plasma levels of von Willebrand factor (VWF)-cleaving protease (ADAMTS13) activity that are within a broad normal range. We investigated the mechanism of initial platelet accumulation on Stx-stimulated endothelial cells. Stx-1 or Stx-2 (1-10 nM) stimulated the rapid secretion of unusually large (UL) VWF multimeric strings from human umbilical vein endothelial cells (HUVECs) or human glomerular microvascular endothelial cells (GMVECs). Perfused normal human platelets immediately adhered to the secreted ULVWF multimeric strings. Nanomolar concentrations (1-10 nM) of the Shiga toxins were as effective in inducing the formation of ULVWF-platelet strings as millimolar concentrations (0.1-20 mM) of histamine. The rate of ULVWF-platelet string cleavage by plasma or recombinant ADAMTS13 was delayed by 3 to 10 minutes (or longer) in the presence of 10 nM Stx-1 or Stx-2 compared with 20 mM histamine. Stx-induced formation of ULVWF strings, and impairment of ULVWF-platelet string cleavage by ADAMTS13, may promote initial platelet adhesion above glomerular endothelial cells. These processes may contribute to the evolution of glomerular occlusion by platelet and fibrin thrombi in diarrhea-associated HUS.
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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.