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Thrombin-derived host defence peptide modulates neutrophil rolling and migration in vitro and functional response in vivo

Lim, Chun Hwee; Puthia, Manoj LU ; Butrym, Marta LU ; Tay, Hui Min; Lee, Michelle Zi Yi; Hou, Han Wei and Schmidtchen, Artur LU (2017) In Scientific Reports 7(1).
Abstract

Host defence peptides (HDPs) derived from the C-terminus of thrombin are proteolytically generated by enzymes released during inflammation and wounding. In this work, we studied the effects of the prototypic peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), on neutrophil functions. In vitro, GKY25 was shown to decrease LPS-induced neutrophil activation. In addition, the peptide induced CD62L shedding on neutrophils without inducing their activation. Correspondingly, GKY25-treated neutrophils showed reduced attachment and rolling behaviour on surfaces coated with the CD62L ligand E-selectin. The GKY25-treated neutrophils also displayed a dampened chemotactic response against the chemokine IL-8. Furthermore, in vivo, mice treated with GKY25... (More)

Host defence peptides (HDPs) derived from the C-terminus of thrombin are proteolytically generated by enzymes released during inflammation and wounding. In this work, we studied the effects of the prototypic peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), on neutrophil functions. In vitro, GKY25 was shown to decrease LPS-induced neutrophil activation. In addition, the peptide induced CD62L shedding on neutrophils without inducing their activation. Correspondingly, GKY25-treated neutrophils showed reduced attachment and rolling behaviour on surfaces coated with the CD62L ligand E-selectin. The GKY25-treated neutrophils also displayed a dampened chemotactic response against the chemokine IL-8. Furthermore, in vivo, mice treated with GKY25 exhibited a reduced local ROS response against LPS. Taken together, our results show that GKY25 can modulate neutrophil functions in vitro and in vivo.

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Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
7
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85029349882
  • wos:000410064000037
ISSN
2045-2322
DOI
10.1038/s41598-017-11464-x
language
English
LU publication?
yes
id
d95a2b7e-0b36-4bde-99d1-e2f2ce58503f
date added to LUP
2017-09-29 07:14:36
date last changed
2018-01-16 13:19:50
@article{d95a2b7e-0b36-4bde-99d1-e2f2ce58503f,
  abstract     = {<p>Host defence peptides (HDPs) derived from the C-terminus of thrombin are proteolytically generated by enzymes released during inflammation and wounding. In this work, we studied the effects of the prototypic peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), on neutrophil functions. In vitro, GKY25 was shown to decrease LPS-induced neutrophil activation. In addition, the peptide induced CD62L shedding on neutrophils without inducing their activation. Correspondingly, GKY25-treated neutrophils showed reduced attachment and rolling behaviour on surfaces coated with the CD62L ligand E-selectin. The GKY25-treated neutrophils also displayed a dampened chemotactic response against the chemokine IL-8. Furthermore, in vivo, mice treated with GKY25 exhibited a reduced local ROS response against LPS. Taken together, our results show that GKY25 can modulate neutrophil functions in vitro and in vivo.</p>},
  articleno    = {11201},
  author       = {Lim, Chun Hwee and Puthia, Manoj and Butrym, Marta and Tay, Hui Min and Lee, Michelle Zi Yi and Hou, Han Wei and Schmidtchen, Artur},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Thrombin-derived host defence peptide modulates neutrophil rolling and migration in vitro and functional response in vivo},
  url          = {http://dx.doi.org/10.1038/s41598-017-11464-x},
  volume       = {7},
  year         = {2017},
}