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Thrombin and plasmin alter the proteome of neutrophil extracellular traps

Lim, Chun Hwee; Adav, Sunil S.; Sze, Siu Kwan; Choong, Yeu Khai; Saravanan, Rathi and Schmidtchen, Artur LU (2018) In Frontiers in Immunology 9(JUL).
Abstract

Neutrophil extracellular traps (NETs) consist of a decondensed DNA scaffold decorated with neutrophil-derived proteins. The proteome of NETs, or "NETome," has been largely elucidated in vitro. However, components such as plasma and extracellular matrix proteins may affect the NETome under physiological conditions. Here, using a reductionistic approach, we explored the effects of two proteases active during injury and wounding, human thrombin and plasmin, on the NETome. Using high-resolution mass spectrometry, we identified a total of 164 proteins, including those previously not described in NETs. The serine proteases, particularly thrombin, were also found to interact with DNA and bound to NETs in vitro. Among the most abundant proteins... (More)

Neutrophil extracellular traps (NETs) consist of a decondensed DNA scaffold decorated with neutrophil-derived proteins. The proteome of NETs, or "NETome," has been largely elucidated in vitro. However, components such as plasma and extracellular matrix proteins may affect the NETome under physiological conditions. Here, using a reductionistic approach, we explored the effects of two proteases active during injury and wounding, human thrombin and plasmin, on the NETome. Using high-resolution mass spectrometry, we identified a total of 164 proteins, including those previously not described in NETs. The serine proteases, particularly thrombin, were also found to interact with DNA and bound to NETs in vitro. Among the most abundant proteins were those identified previously, including histones, neutrophil elastase, and antimicrobial proteins. We observed reduced histone (H2B, H3, and H4) and neutrophil elastase levels upon the addition of the two proteases. Analyses of NET-derived tryptic peptides identified subtle changes upon protease treatments. Our results provide evidence that exogenous proteases, present during wounding and inflammation, influence the NETome. Taken together, regulation of NETs and their proteins under different physiological conditions may affect their roles in infection, inflammation, and the host response.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Histones, Neutrophil elastase, Neutrophil extracellular traps, Plasmin, Proteome, Thrombin
in
Frontiers in Immunology
volume
9
issue
JUL
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85049632765
DOI
10.3389/fimmu.2018.01554
language
English
LU publication?
yes
id
acd4fd7c-2dfc-41dc-bdc0-669584e1e040
date added to LUP
2018-07-20 11:47:31
date last changed
2019-02-20 11:22:37
@article{acd4fd7c-2dfc-41dc-bdc0-669584e1e040,
  abstract     = {<p>Neutrophil extracellular traps (NETs) consist of a decondensed DNA scaffold decorated with neutrophil-derived proteins. The proteome of NETs, or "NETome," has been largely elucidated in vitro. However, components such as plasma and extracellular matrix proteins may affect the NETome under physiological conditions. Here, using a reductionistic approach, we explored the effects of two proteases active during injury and wounding, human thrombin and plasmin, on the NETome. Using high-resolution mass spectrometry, we identified a total of 164 proteins, including those previously not described in NETs. The serine proteases, particularly thrombin, were also found to interact with DNA and bound to NETs in vitro. Among the most abundant proteins were those identified previously, including histones, neutrophil elastase, and antimicrobial proteins. We observed reduced histone (H2B, H3, and H4) and neutrophil elastase levels upon the addition of the two proteases. Analyses of NET-derived tryptic peptides identified subtle changes upon protease treatments. Our results provide evidence that exogenous proteases, present during wounding and inflammation, influence the NETome. Taken together, regulation of NETs and their proteins under different physiological conditions may affect their roles in infection, inflammation, and the host response.</p>},
  articleno    = {1554},
  author       = {Lim, Chun Hwee and Adav, Sunil S. and Sze, Siu Kwan and Choong, Yeu Khai and Saravanan, Rathi and Schmidtchen, Artur},
  keyword      = {Histones,Neutrophil elastase,Neutrophil extracellular traps,Plasmin,Proteome,Thrombin},
  language     = {eng},
  month        = {07},
  number       = {JUL},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Immunology},
  title        = {Thrombin and plasmin alter the proteome of neutrophil extracellular traps},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.01554},
  volume       = {9},
  year         = {2018},
}