Статья

Neutrophil extracellular traps in COVID-19

Yu ZuoDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USASrilakshmi YalavarthiDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USAHui ShiDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USAKelsey GockmanDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USAMelanie ZuoJacqueline A. MadisonDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USAChristopher BlairDivision of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USAAndrew WeberDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Northwell Health, New York, New York, USABetsy BarnesCenter for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USAMikala EgebladCold Spring Harbor Laboratory, Cold Spring Harbor, New York, USARobert J. WoodsDivision of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USAYogendra KanthiDivision of Cardiology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USAJason S. KnightDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

2020en

ABI

Аннотация

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.

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Идентификаторы

DOI: 10.1172/jci.insight.138999

Цитирования и источники

Цитирований: 3Использованных источников: 0

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