ArticleAnnals of the rheumatic diseases2017
Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis.
Article in Annals of the rheumatic diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Neutrophil Extracellular Traps (NETs) and Vasculitis.International journal of medical sciences · 2021Pooled it
- Neutrophils and Platelets as Key Players in the Pathogenesis of ANCA-Associated Vasculitis and Potential Sources of Disease Activity Biomarkers.Diagnostics (Basel, Switzerland) · 2025Review
- Neutrophils and NETs in kidney disease.Nature reviews. Nephrology · 2025Review
- Research Advances in the Immunomodulatory Functions of CD100/SEMA4D and Their Roles in Viral Infectious Diseases.International journal of molecular sciences · 2025Review
- Neutrophils in Tissue Injury and Repair: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Biomarkers in ANCA associated vasculitis: clinical utility, pitfalls and their role in the outcomes assessment.Frontiers in immunology · 2025Review
- Semaphorin heterodimerization in cis regulates membrane targeting and neocortical wiring.Nature communications · 2024Article
- Soluble Semaphorin 4D Serum Concentrations Are Elevated in Critically Ill Patients with Liver Cirrhosis and Correlate with Aminotransferases.Diagnostics (Basel, Switzerland) · 2024Article
- New Promising Routes in Peptic Ulcers: Toll-like Receptors and Semaphorins.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Plexin-mediated neuronal development and neuroinflammatory responses in the nervous system.Histology and histopathology · 2023Review
- The value of serum Sema4D level in predicting the prognosis of patients with acute ST-segment elevation myocardial infarction and with high thrombus burden.BMC cardiovascular disorders · 2023Article
- The value of serum Sema4D level in reflecting the inflammatory state of acute ST-segment elevation myocardial infarction.Journal of thoracic disease · 2023Article
- [Ascites CD100 levels and immunomodulation effects in the peripheral blood of patients with liver cirrhosis combined with spontaneous bacterial peritonitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Semaphorins in immune cell function, inflammatory and infectious diseases.Current research in immunology · 2023Review
- The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.Journal of immunology research · 2023Article
- The involvement of NETs in ANCA-associated vasculitis.Frontiers in immunology · 2023Review
- Platelet formation and activation are influenced by neuronal guidance proteins.Frontiers in immunology · 2023Review
- Do Semaphorins Play a Role in Development of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease?Biomedicines · 2022Article
- Muscone Can Improve Spinal Cord Injury by Activating the Angiogenin/Plexin-B2 Axis.Molecular neurobiology · 2022Review
- Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesInappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to investigate the functions of semaphorin 4D (SEMA4D) in regulation of neutrophil activation, and its involvement in AAV pathogenesis.
methodsSerum levels of soluble SEMA4D were evaluated by ELISA. Blood cell-surface expression of membrane SEMA4D was evaluated by flow cytometry. To determine the functional interactions between neutrophil membrane SEMA4D and endothelial plexin B2, wild-type and
resultsSerum levels of soluble SEMA4D were elevated in patients with AAV and correlated with disease activity scores. Cell-surface expression of SEMA4D was downregulated in neutrophils from patients with AAV, a consequence of proteolytic cleavage of membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. Recombinant plexin B2 suppressed neutrophil Rac1 activation through SEMA4D's intracellular domain, and inhibited pathogen-induced or ANCA-induced oxidative burst and NET formation.
conclusionsNeutrophil surface SEMA4D functions as a negative regulator of neutrophil activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising biomarker and potential therapeutic target for AAV.
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