Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation
نویسندگان
چکیده
AbstractBackground Coagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) associated with increased mortality. Clinical experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation poorly understood. Methods We performed proteomic analysis immunostaining postmortem lung tissues from patients other pathologies. further compared coagulation factor XII (FXII) DNase activities plasma samples healthy control donors determined NET-induced FXII activation using chromogenic substrate assay. Findings expression activity were the parenchyma, within pulmonary vasculature fibrin-rich alveolar spaces patients. In agreement this, plasmaaac acafajföeFXII (FXIIa) was Furthermore, FXIIa colocalized NETs tissue indicating accumulation leads to contact COVID-19. showed an is partially due impaired NET clearance by DNases as substitution improved dissolution reduced in vitro. Interpretation Collectively, our study supports NET/FXII axis contributes pathogenic chain procoagulant proinflammatory responses Targeting both may offer potential novel therapeutic strategy. Funding This supported European Union (840189), Werner Otto Medical Foundation Hamburg (8/95) German Research (FR4239/1-1, A11/SFB877, B08/SFB841 P06/KFO306).
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ژورنال
عنوان ژورنال: EBioMedicine
سال: 2021
ISSN: ['2352-3964']
DOI: https://doi.org/10.1016/j.ebiom.2021.103382