Rapid high-throughput method for investigating physiological regulation of neutrophil extracellular trap formation

Zukas, Kieran; Cayford, Justin; Serneo, Finley; Atteberry, Brandi; Retter, Andrew; Eccleston, Mark; Kelly, Theresa K.

doi:10.1016/j.jtha.2024.05.028

Journal of Thrombosis and Haemostasis

2024

DOI: 10.1016/j.jtha.2024.05.028

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Rapid high-throughput method for investigating physiological regulation of neutrophil extracellular trap formation

Kieran Zukas,

Justin Cayford,

Finley Serneo

et al.

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Cutting the Gordian knot of neutrophil extracellular traps research

Denorme

2024

Journal of Thrombosis and Haemostasis

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Cutting the Gordian knot of neutrophil extracellular traps research

Denorme

2024

Journal of Thrombosis and Haemostasis

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Understanding the complex chromatin dynamics in primary human neutrophils during PMA-induced NET formation

Atteberry,

Berman,

Kelly

et al. 2024

Front. Immunol.

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BackgroundPrimary human neutrophils play a pivotal role in innate immunity, mainly through the formation of neutrophil extracellular traps (NETs) in a process known as NETosis. This cell-death pathway is crucial for combating infections but is also implicated in many inflammatory diseases, such as sepsis, systemic lupus erythematosus, and rheumatoid arthritis.MethodsThe study presented here investigates chromatin dynamics during NET formation by stimulating primary human neutrophils with phorbol 12-myristate 13-acetate (PMA). We adapt the ATAC-Seq (assay for transposase-accessible chromatin using sequencing) method to isolated neutrophils and characterize a time-dependent chromatin response.ResultsWe found that chromatin accessibility patterns are consistent across individual donors and most chromatin changes occur within 30 min, with many continuing across the 90 min assessed in this study. Regulatory regions gaining accessibility were associated with the activity of pathways that have been implicated in NOX-dependent NET formation.ConclusionsOur findings increase the understanding of the chromatin changes underlying NET formation and also identify potential early-acting targets for modulating this process in inflammatory diseases.

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Rapid high-throughput method for investigating physiological regulation of neutrophil extracellular trap formation

Cited by 2 publications

References 28 publications

Cutting the Gordian knot of neutrophil extracellular traps research

Cutting the Gordian knot of neutrophil extracellular traps research

Understanding the complex chromatin dynamics in primary human neutrophils during PMA-induced NET formation

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