Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin

Rebecca Dowey; Joby Cole; A. A. Roger Thompson; Rebecca Hull; Chenghao Huang; Jacob Whatmore; Ahmed Iqbal; Kirsty Bradley; Joanne McKenzie; Allan  Lawrie; Alison M. Condliffef; Endre  Kiss-Toth; Ian Sabroe; Lynne R. Prince

doi:10.1183/23120541.00596-2021

Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin

Rebecca Dowey, Joby Cole, A. A. Roger Thompson, Rebecca Hull, Chenghao Huang, Jacob Whatmore, Ahmed Iqbal, Kirsty Bradley, Joanne McKenzie, Allan Lawrie, Alison M. Condliffef, Endre Kiss-Toth, Ian Sabroe, Lynne R. Prince

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

Neutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in coronavirus disease 2019 (COVID-19) and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients.

Methods
Neutrophils were isolated from healthy volunteers (n=9) and hospitalised patients with COVID-19 at the acute stage (n=39) and again at 3–4 months post-acute sampling (n=7). NETosis was measured by SYTOX green assays.

Results
Here, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to lipopolysaccharide (LPS) compared to cells from healthy control subjects. A subset of patients was captured at follow-up clinics (3–4 months post-acute sampling), and while LPS-induced NET formation is significantly lower at this time po

Original language	English
Article number	00596-2021
Number of pages	13
Journal	ERJ Open Research
Volume	8
Issue number	2
DOIs	https://doi.org/10.1183/23120541.00596-2021
Publication status	Published - 1 Apr 2022
Externally published	Yes

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10.1183/23120541.00596-2021Licence: CC BY

Cite this

Dowey, R., Cole, J., Thompson, A. A. R., Hull, R., Huang, C., Whatmore, J., Iqbal, A., Bradley, K., McKenzie, J., Lawrie, A., Condliffef, A. M., Kiss-Toth, E., Sabroe, I., & Prince, L. R. (2022). Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin. ERJ Open Research, 8(2), [00596-2021]. https://doi.org/10.1183/23120541.00596-2021

@article{6bd988d41dc4451a90698999d5333ba6,

title = "Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin",

abstract = "Neutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in coronavirus disease 2019 (COVID-19) and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients.MethodsNeutrophils were isolated from healthy volunteers (n=9) and hospitalised patients with COVID-19 at the acute stage (n=39) and again at 3–4 months post-acute sampling (n=7). NETosis was measured by SYTOX green assays.ResultsHere, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to lipopolysaccharide (LPS) compared to cells from healthy control subjects. A subset of patients was captured at follow-up clinics (3–4 months post-acute sampling), and while LPS-induced NET formation is significantly lower at this time po",

keywords = "Neutrophil function, NETosis, Covid 19, Ruboxistaurin",

author = "Rebecca Dowey and Joby Cole and Thompson, {A. A. Roger} and Rebecca Hull and Chenghao Huang and Jacob Whatmore and Ahmed Iqbal and Kirsty Bradley and Joanne McKenzie and Allan Lawrie and Condliffef, {Alison M.} and Endre Kiss-Toth and Ian Sabroe and Prince, {Lynne R.}",

year = "2022",

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day = "1",

doi = "10.1183/23120541.00596-2021",

language = "English",

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journal = "ERJ Open Research",

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Dowey, R, Cole, J, Thompson, AAR, Hull, R, Huang, C, Whatmore, J, Iqbal, A, Bradley, K, McKenzie, J, Lawrie, A, Condliffef, AM, Kiss-Toth, E, Sabroe, I & Prince, LR 2022, 'Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin', ERJ Open Research, vol. 8, no. 2, 00596-2021. https://doi.org/10.1183/23120541.00596-2021

TY - JOUR

T1 - Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin

AU - Dowey, Rebecca

AU - Cole, Joby

AU - Thompson, A. A. Roger

AU - Hull, Rebecca

AU - Huang, Chenghao

AU - Whatmore, Jacob

AU - Iqbal, Ahmed

AU - Bradley, Kirsty

AU - McKenzie, Joanne

AU - Lawrie, Allan

AU - Condliffef, Alison M.

AU - Kiss-Toth, Endre

AU - Sabroe, Ian

AU - Prince, Lynne R.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - Neutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in coronavirus disease 2019 (COVID-19) and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients.MethodsNeutrophils were isolated from healthy volunteers (n=9) and hospitalised patients with COVID-19 at the acute stage (n=39) and again at 3–4 months post-acute sampling (n=7). NETosis was measured by SYTOX green assays.ResultsHere, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to lipopolysaccharide (LPS) compared to cells from healthy control subjects. A subset of patients was captured at follow-up clinics (3–4 months post-acute sampling), and while LPS-induced NET formation is significantly lower at this time po

AB - Neutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in coronavirus disease 2019 (COVID-19) and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients.MethodsNeutrophils were isolated from healthy volunteers (n=9) and hospitalised patients with COVID-19 at the acute stage (n=39) and again at 3–4 months post-acute sampling (n=7). NETosis was measured by SYTOX green assays.ResultsHere, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to lipopolysaccharide (LPS) compared to cells from healthy control subjects. A subset of patients was captured at follow-up clinics (3–4 months post-acute sampling), and while LPS-induced NET formation is significantly lower at this time po

KW - Neutrophil function

KW - NETosis

KW - Covid 19

KW - Ruboxistaurin

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