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10.1016/j.ebiom.2021.103382 http://scihub22266oqcxt.onion/10.1016/j.ebiom.2021.103382 34000623!8120108!34000623     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       EBioMedicine 2021 ; 67 (ä): 103382 Nephropedia Template TP {{tp|p=34000623|t=2021. Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation |pdf=|usr=}}{{34000623}} gab.com Text Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation JO: EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=34000623 #FOAvip BACKGROUND: Coagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. METHODS: We performed proteomic analysis and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We further compared coagulation factor XII (FXII) and DNase activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced FXII activation using a chromogenic substrate assay. FINDINGS: FXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients. In agreement with this, plasmaaac acafajfoeFXII activation (FXIIa) was increased in samples from COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially due to impaired NET clearance by extracellular DNases as DNase substitution improved NET dissolution and reduced FXII activation in vitro. INTERPRETATION: Collectively, our study supports that the NET/FXII axis contributes to the pathogenic chain of procoagulant and proinflammatory responses in COVID-19. Targeting both NETs and FXIIa may offer a potential novel therapeutic strategy. FUNDING: This study was supported by the European Union (840189), the Werner Otto Medical Foundation Hamburg (8/95) and the German Research Foundation (FR4239/1-1, A11/SFB877, B08/SFB841 and P06/KFO306). Twit Text FOAVip Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation ????EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=34000623 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34000623 #FOAvip English Wikipedia <ref>{{Cite pmid|34000623}}</ref> Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation #MMPMID34000623 Englert H; Rangaswamy C; Deppermann C; Sperhake JP; Krisp C; Schreier D; Gordon E; Konrath S; Haddad M; Pula G; Mailer RK; Schluter H; Kluge S; Langer F; Puschel K; Panousis K; Stavrou EX; Maas C; Renne T; Frye M EBioMedicine 2021[May]; 67 (ä): 103382 PMID34000623show ga BACKGROUND: Coagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. METHODS: We performed proteomic analysis and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We further compared coagulation factor XII (FXII) and DNase activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced FXII activation using a chromogenic substrate assay. FINDINGS: FXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients. In agreement with this, plasmaaac acafajfoeFXII activation (FXIIa) was increased in samples from COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially due to impaired NET clearance by extracellular DNases as DNase substitution improved NET dissolution and reduced FXII activation in vitro. INTERPRETATION: Collectively, our study supports that the NET/FXII axis contributes to the pathogenic chain of procoagulant and proinflammatory responses in COVID-19. Targeting both NETs and FXIIa may offer a potential novel therapeutic strategy. FUNDING: This study was supported by the European Union (840189), the Werner Otto Medical Foundation Hamburg (8/95) and the German Research Foundation (FR4239/1-1, A11/SFB877, B08/SFB841 and P06/KFO306). |Autopsy[MESH] |COVID-19/*metabolism[MESH] |Case-Control Studies[MESH] |Deoxyribonucleases/blood/metabolism[MESH] |Extracellular Traps/*metabolism[MESH] |Factor XII/*metabolism[MESH] |Humans[MESH] |Lung/metabolism[MESH] |Neutrophil Activation[MESH] |Pneumonia[MESH]Defective NET clearance contributes to sustained FXII activation in C(epmc).pdf DeepDyve Pubget Overpricing