ArticleBlood2016
Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 76 citations in OpenAlex.
- Biological attributes of zinc-dependent endopeptidases in endothelial dysfunction associated with sepsis: a narrative review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Article
- Evaluating the potential for iodinated radiocontrast agents to interfere with ADAMTS13 activity testing via fluorescence resonance energy transfer methodology.American journal of clinical pathology · 2025Article
- Systemic Inflammatory Response Syndrome, Thromboinflammation, and Septic Shock in Fetuses and Neonates.International journal of molecular sciences · 2025Review
- HNP-1: From Structure to Application Thanks to Multifaceted Functions.Microorganisms · 2025Review
- Overall leukocyte levels link risk factors to Von Willebrand factor and Neutrophil Extracellular Traps in stroke thrombi: a Structural Equation Modeling analysis.Frontiers in neurology · 2025Article
- Novel functions for von Willebrand factor.Blood · 2024Review
- The Phenomenon of Thrombotic Microangiopathy in Cancer Patients.International journal of molecular sciences · 2024Review
- Regulation of von Willebrand factor by ADAMTS13 ameliorates lipopolysaccharide-induced lung injury in mice.International journal of hematology · 2023Article
- A Global Assessment of Coagulation Profile and a Novel Insight into Adamts-13 Implication in Neonatal Sepsis.Biology · 2023Article
- ADAMTS13 and Non-ADAMTS13 Biomarkers in Immune-Mediated Thrombotic Thrombocytopenic Purpura.Journal of clinical medicine · 2023Review
- ADAMTS13 Biomarkers in Management of Immune Thrombotic Thrombocytopenic Purpura.Archives of pathology & laboratory medicine · 2023Review
- A new ferroptosis-related signature model including messenger RNAs and long non-coding RNAs predicts the prognosis of gastric cancer patients.Journal of translational internal medicine · 2023Article
- Mechanisms of ADAMTS13 regulation.Journal of thrombosis and haemostasis : JTH · 2022Review
- Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation.Matrix biology plus · 2022Review
- Associations between the von Willebrand Factor-ADAMTS13 Axis, Complement Activation, and COVID-19 Severity and Mortality.Thrombosis and haemostasis · 2022Article
- Neutrophils as Regulators and Biomarkers of Cardiovascular Inflammation in the Context of Abdominal Aortic Aneurysms.Biomedicines · 2021Review
- Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors.Biomolecules · 2021Article
- CanineBiology · 2021Article
- Ferroptosis-Related Genes in Bronchoalveolar Lavage Fluid Serves as Prognostic Biomarkers for Idiopathic Pulmonary Fibrosis.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Infection or inflammation may precede and trigger formation of microvascular thrombosis in patients with acquired thrombotic thrombocytopenic purpura (TTP). However, the mechanism underlying this clinical observation is not fully understood. Here, we show that human neutrophil peptides (HNPs) released from activated and degranulated neutrophils inhibit proteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 in a concentration-dependent manner. Half-maximal inhibitory concentrations of native HNPs toward ADAMTS13-mediated proteolysis of peptidyl VWF73 and multimeric VWF are 3.5 μM and 45 μM, respectively. Inhibitory activity of HNPs depends on the RRY motif that is shared by the spacer domain of ADAMTS13. Native HNPs bind to VWF73 (KD = 0.72 μM), soluble VWF (KD = 0.58 μM), and ultra-large VWF on endothelial cells. Enzyme-linked immunosorbent assay (ELISA) demonstrates markedly increased plasma HNPs1-3 in most patients with acquired autoimmune TTP at presentation (median, ∼170 ng/mL; range, 58-3570; n = 19) compared with healthy controls (median, ∼23 ng/mL; range, 6-44; n = 18) (P < .0001). Liquid chromatography plus tandem mass spectrometry (LC-MS/MS) reveals statistically significant increases of HNP1, HNP2, and HNP3 in patient samples (all P values <.001). There is a good correlation between measurement of HNPs1-3 by ELISA and by LC-MS/MS (Spearman ρ = 0.7932, P < .0001). Together, these results demonstrate that HNPs1-3 may be potent inhibitors of ADAMTS13 activity, likely by binding to the central A2 domain of VWF and physically blocking ADAMTS13 binding. Our findings may provide a novel link between inflammation/infection and the onset of microvascular thrombosis in acquired TTP and potentially other immune thrombotic disorders.
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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.