ArticleCritical care (London, England)2021
Carboxypeptidase B blocks ex vivo activation of the anaphylatoxin-neutrophil extracellular trap axis in neutrophils from COVID-19 patients.
Article in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- Safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of STSA-1002, recombinant anti-human C5a fully human monoclonal antibody, in a randomized, first-in-human phase I study in healthy adults.Frontiers in pharmacology · 2026Trial
- Association of Carboxypeptidase B2 Gene Polymorphisms With Graft Loss in Kidney Transplantation.Transplantation direct · 2026Article
- Mechanisms and impact of long COVID: pathophysiology, neuropsychiatric effects and vaccination.Frontiers in immunology · 2026Review
- Identification of a Prognostic Gene Signature Based on Lenvatinib Resistance in Hepatocellular Carcinoma with Functional Validation of the Key Gene CPB2.Journal of hepatocellular carcinoma · 2026Article
- Complement Activation is More Pronounced in the Kidneys of Critically Ill Patients With COVID-19 Than in Those With Bacterial Sepsis.Kidney international reports · 2025Article
- An anti-complement homogeneous polysaccharide fromActa pharmaceutica Sinica. B · 2025Article
- Article
- Effect of COVID-19 on Thrombosis Incidence and Patient Prognosis in Kidney Transplant Recipients.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- Simple and Scalable Algorithms for Cluster-Aware Precision Medicine.Proceedings of machine learning research · 2024Article
- Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation.International journal of nanomedicine · 2024Review
- The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies.Biomedicines · 2023Article
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
- Identification of Protein Quality Markers in Toad Venom fromMolecules (Basel, Switzerland) · 2023Article
- Understanding COVID-19-associated coagulopathy.Nature reviews. Immunology · 2022Review
- Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium.Nature reviews. Cardiology · 2022Review
- Neutrophil subsets and their differential roles in viral respiratory diseases.Journal of leukocyte biology · 2022Review
- Use of nCounter mRNA profiling to identify at-arrival gene expression patterns for predicting bovine respiratory disease in beef cattle.BMC veterinary research · 2022Article
- The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.Signal transduction and targeted therapy · 2022Review
- ICODE: the international COVID-19 thrombosis biomarkers colloquium-novel soluble biomarkers: circulating cell-free nucleic acids and other molecules.Journal of thrombosis and thrombolysis · 2022Article
- NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThrombosis and coagulopathy are highly prevalent in critically ill patients with COVID-19 and increase the risk of death. Immunothrombosis has recently been demonstrated to contribute to the thrombotic events in COVID-19 patients with coagulopathy. As the primary components of immunothrombosis, neutrophil extracellular traps (NETs) could be induced by complement cascade components and other proinflammatory mediators. We aimed to explore the clinical roles of NETs and the regulation of complement on the NET formation in COVID-19.
methodsWe recruited 135 COVID-19 patients and measured plasma levels of C5, C3, cell-free DNA and myeloperoxidase (MPO)-DNA. Besides, the formation of NETs was detected by immunofluorescent staining and the cytotoxicity to vascular endothelial HUVEC cells was evaluated by CCK-8 assay.
resultsWe found that the plasma levels of complements C3 and MPO-DNA were positively related to coagulation indicator fibrin(-ogen) degradation products (C3: r = 0.300, p = 0.005; MPO-DNA: r = 0.316, p = 0.002) in COVID-19 patients. Besides, C3 was positively related to direct bilirubin (r = 0.303, p = 0.004) and total bilirubin (r = 0.304, p = 0.005), MPO-DNA was positively related to lactate dehydrogenase (r = 0.306, p = 0.003) and creatine kinase (r = 0.308, p = 0.004). By using anti-C3a and anti-C5a antibodies, we revealed that the complement component anaphylatoxins in the plasma of COVID-19 patients strongly induced NET formation. The pathological effect of the anaphylatoxin-NET axis on the damage of vascular endothelial cells could be relieved by recombinant carboxypeptidase B (CPB), a stable homolog of enzyme CPB2 which can degrade anaphylatoxins to inactive products.
conclusionsOver-activation in anaphylatoxin-NET axis plays a pathological role in COVID-19. Early intervention in anaphylatoxins might help prevent thrombosis and disease progression in COVID-19 patients.
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