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10.1172/JCI141374

http://scihub22266oqcxt.onion/10.1172/JCI141374
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32759504!7598040!32759504
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suck abstract from ncbi


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pmid32759504      J+Clin+Invest 2020 ; 130 (11): 6151-6157
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  • Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis #MMPMID32759504
  • Skendros P; Mitsios A; Chrysanthopoulou A; Mastellos DC; Metallidis S; Rafailidis P; Ntinopoulou M; Sertaridou E; Tsironidou V; Tsigalou C; Tektonidou M; Konstantinidis T; Papagoras C; Mitroulis I; Germanidis G; Lambris JD; Ritis K
  • J Clin Invest 2020[Nov]; 130 (11): 6151-6157 PMID32759504show ga
  • Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.
  • |*Betacoronavirus/immunology/metabolism[MESH]
  • |*Complement Membrane Attack Complex/immunology/metabolism[MESH]
  • |*Coronavirus Infections/blood/immunology[MESH]
  • |*Extracellular Traps/immunology/metabolism[MESH]
  • |*Neutrophils/immunology/metabolism[MESH]
  • |*Pandemics[MESH]
  • |*Pneumonia, Viral/blood/immunology[MESH]
  • |*Thromboplastin/immunology/metabolism[MESH]
  • |*Thrombosis/blood/immunology/virology[MESH]
  • |Aged[MESH]
  • |COVID-19[MESH]
  • |Complement Activation/drug effects[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Peptides, Cyclic/pharmacology[MESH]
  • |Receptor, Anaphylatoxin C5a/antagonists & inhibitors/blood/immunology[MESH]
  • |Respiratory Distress Syndrome/blood/immunology/virology[MESH]
  • |SARS-CoV-2[MESH]


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