{"doi":"10.3389/fimmu.2020.610696","title":"Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13","abstract":"<jats:p>Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.</jats:p>","journal":"Frontiers in Immunology","year":2020,"id":593702,"datarank":0.7156026936698499,"base_score":4.770684624465665,"endowment":4.770684624465665,"self_citation_contribution":0.7156026936698499,"citation_network_contribution":0.0,"self_endowment_contribution":0.7156026936698499,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":117,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1519616,"name":"Zhiwei Wu","orcid":"0009-0001-3777-8997","position":1,"is_corresponding":false},{"id":27519,"name":"Quan Long","orcid":"0000-0003-3795-1873","position":2,"is_corresponding":false},{"id":640913,"name":"Jiaqi Huang","orcid":"0000-0001-7144-685X","position":3,"is_corresponding":false},{"id":1519617,"name":"Tiantian Hong","orcid":null,"position":4,"is_corresponding":false},{"id":336602,"name":"Wang Liu","orcid":"0000-0002-5286-114X","position":5,"is_corresponding":false},{"id":1519618,"name":"Jiangguo Lin","orcid":null,"position":6,"is_corresponding":false},{"id":1519615,"name":"Junxian Yang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13","abstract":"<jats:p>Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.</jats:p>","is_dataset_classified":null,"base_score":4.770684624465665,"endowment":4.770684624465665,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33343584","pmcid":"PMC7738460","openalex_id":"https://openalex.org/W3107984200","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"31771012","title":null},{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"PTDC/CCI-BIO/29266/2017","title":"Deep Drug Discovery and Deployment"}],"total_grants":2,"fwci":4.01,"citation_percentile":0.95200822,"influential_citations":0,"citation_trend":[{"year":2021,"count":16},{"year":2022,"count":24},{"year":2023,"count":16},{"year":2024,"count":23},{"year":2025,"count":18},{"year":2026,"count":20}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2020.610696/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2020.610696/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2020.610696/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fimmu.2020.610696","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33343584","host_type":"repository"},{"url":"https://doaj.org/article/9b67522bb9934706b685b2e0200d98dd","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7738460","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7738460","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7738460?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3389/fimmu.2020.610696","host_type":""},{"url":"https://dx.doi.org/10.3389/fimmu.2020.610696","host_type":""}],"fields_of_study":["Neutrophil, Myeloperoxidase and Oxidative Mechanisms","Complement system in diseases","Vasculitis and related conditions","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["ADAMTS13 Protein","COVID-19","SARS-CoV-2","Acute Disease","Brain Ischemia","Humans","Thrombosis","von Willebrand Factor","Stroke","Thrombotic Microangiopathies","Extracellular Traps"],"keywords":["ADAMTS13","Von Willebrand factor","Neutrophil extracellular traps","Thrombospondin","Inflammation","Disintegrin","Metalloproteinase","Platelet","Platelet activation","Immunology","Medicine","Cell biology","Internal medicine","Matrix metalloproteinase","Biology","Acute Ischemic Stroke","Thrombotic Microangiopathy","Covid-19","SARS-CoV-2","Thrombotic Microangiopathies","ADAMTS13 Protein","Thrombosis","RC581-607","Extracellular Traps","Brain Ischemia","Stroke","Acute Disease","Humans","Immunologic diseases. Allergy"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.26952358.v1","title":"Additional file 1 of Circulating microRNAs targeting coagulation and fibrinolysis in patients with severe COVID-19","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26952358","title":"Additional file 1 of Circulating microRNAs targeting coagulation and fibrinolysis in patients with severe COVID-19","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T11:57:08.963518Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}