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Thrombin-derived host-defense peptides modulate monocyte/macrophage inflammatory responses to gram-negative bacteria

Hansen, Finja C. LU ; Strömdahl, Ann Charlotte LU ; Mörgelin, Matthias LU ; Schmidtchen, Artur LU and van der Plas, Mariena J.A. LU (2017) In Frontiers in Immunology 8(JUL).
Abstract

Host-defense peptides play a fundamental role in the innate immune system by modulating inflammatory responses. Previously, it was shown that the thrombin derived host-defense peptide GKY25 inhibits LPS-induced responses of monocytes and macrophages in vitro, ex vivo, and in vivo. In this study, the effect of GKY25 on the interaction of monocytes/macrophages with Gram-negative bacteria was explored. Electron microscopy analysis showed that fibrin slough from non-healing wounds, colonized with Staphylococcus aureus and Pseudomonas aeruginosa, contains C-terminal thrombin epitopes associated with these bacteria extracellularly and in phagosomes of leukocytes. Live imaging of RAW 264.7 cell cultures showed binding of GKY25 to Escherichia... (More)

Host-defense peptides play a fundamental role in the innate immune system by modulating inflammatory responses. Previously, it was shown that the thrombin derived host-defense peptide GKY25 inhibits LPS-induced responses of monocytes and macrophages in vitro, ex vivo, and in vivo. In this study, the effect of GKY25 on the interaction of monocytes/macrophages with Gram-negative bacteria was explored. Electron microscopy analysis showed that fibrin slough from non-healing wounds, colonized with Staphylococcus aureus and Pseudomonas aeruginosa, contains C-terminal thrombin epitopes associated with these bacteria extracellularly and in phagosomes of leukocytes. Live imaging of RAW 264.7 cell cultures showed binding of GKY25 to Escherichia coli BioParticles extracellularly, and colocalization intracellularly. Although peptide binding did not alter the rate of phagocytosis, GKY25 reduced NF-κB/AP-1 activation and subsequent cytokine release in response to both heat-killed and live bacteria. Notably, preincubation of RAW 264.7 cells with peptide did increase BioParticle uptake in a dose-dependent manner. Taken together, the thrombin-derived host-defense peptide GKY25 binds to bacteria extracellularly and colocalizes with bacteria intracellularly, thereby reducing pro-inflammatory responses.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gram-negative bacteria, Host-defense peptides, Inflammation, Macrophages, Monocytes, Phagocytosis, Thrombin
in
Frontiers in Immunology
volume
8
issue
JUL
article number
843
publisher
Frontiers Media S. A.
external identifiers
  • pmid:28785265
  • wos:000406005300002
  • scopus:85025709662
ISSN
1664-3224
DOI
10.3389/fimmu.2017.00843
project
Host-pathogen interactions and the development of chronic infections
language
English
LU publication?
yes
id
0265b854-35bb-4f6f-a017-e1e005eb5b79
date added to LUP
2017-08-24 16:53:13
date last changed
2025-01-07 19:21:02
@article{0265b854-35bb-4f6f-a017-e1e005eb5b79,
  abstract     = {{<p>Host-defense peptides play a fundamental role in the innate immune system by modulating inflammatory responses. Previously, it was shown that the thrombin derived host-defense peptide GKY25 inhibits LPS-induced responses of monocytes and macrophages in vitro, ex vivo, and in vivo. In this study, the effect of GKY25 on the interaction of monocytes/macrophages with Gram-negative bacteria was explored. Electron microscopy analysis showed that fibrin slough from non-healing wounds, colonized with Staphylococcus aureus and Pseudomonas aeruginosa, contains C-terminal thrombin epitopes associated with these bacteria extracellularly and in phagosomes of leukocytes. Live imaging of RAW 264.7 cell cultures showed binding of GKY25 to Escherichia coli BioParticles extracellularly, and colocalization intracellularly. Although peptide binding did not alter the rate of phagocytosis, GKY25 reduced NF-κB/AP-1 activation and subsequent cytokine release in response to both heat-killed and live bacteria. Notably, preincubation of RAW 264.7 cells with peptide did increase BioParticle uptake in a dose-dependent manner. Taken together, the thrombin-derived host-defense peptide GKY25 binds to bacteria extracellularly and colocalizes with bacteria intracellularly, thereby reducing pro-inflammatory responses.</p>}},
  author       = {{Hansen, Finja C. and Strömdahl, Ann Charlotte and Mörgelin, Matthias and Schmidtchen, Artur and van der Plas, Mariena J.A.}},
  issn         = {{1664-3224}},
  keywords     = {{Gram-negative bacteria; Host-defense peptides; Inflammation; Macrophages; Monocytes; Phagocytosis; Thrombin}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{JUL}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Thrombin-derived host-defense peptides modulate monocyte/macrophage inflammatory responses to gram-negative bacteria}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2017.00843}},
  doi          = {{10.3389/fimmu.2017.00843}},
  volume       = {{8}},
  year         = {{2017}},
}