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Selective protein aggregation confines and inhibits endotoxins in wounds : Linking host defense to amyloid formation

Petrlova, Jitka LU ; Hartman, Erik ; Petruk, Ganna LU orcid ; Lim, Jeremy Chun Hwee LU orcid ; Adav, Sunil Shankar ; Kjellström, Sven LU ; Puthia, Manoj LU and Schmidtchen, Artur LU (2023) In iScience 26(10).
Abstract

Bacterial lipopolysaccharide (LPS) induces rapid protein aggregation in human wound fluid. We aimed to characterize these LPS-induced aggregates and their functional implications using a combination of mass spectrometry analyses, biochemical assays, biological imaging, cell experiments, and animal models. The wound-fluid aggregates encompass diverse protein classes, including sequences from coagulation factors, annexins, histones, antimicrobial proteins/peptides, and apolipoproteins. We identified proteins and peptides with a high aggregation propensity and verified selected components through Western blot analysis. Thioflavin T and Amytracker staining revealed amyloid-like aggregates formed after exposure to LPS in vitro in human wound... (More)

Bacterial lipopolysaccharide (LPS) induces rapid protein aggregation in human wound fluid. We aimed to characterize these LPS-induced aggregates and their functional implications using a combination of mass spectrometry analyses, biochemical assays, biological imaging, cell experiments, and animal models. The wound-fluid aggregates encompass diverse protein classes, including sequences from coagulation factors, annexins, histones, antimicrobial proteins/peptides, and apolipoproteins. We identified proteins and peptides with a high aggregation propensity and verified selected components through Western blot analysis. Thioflavin T and Amytracker staining revealed amyloid-like aggregates formed after exposure to LPS in vitro in human wound fluid and in vivo in porcine wound models. Using NF-κB-reporter mice and IVIS bioimaging, we demonstrate that such wound-fluid LPS aggregates induce a significant reduction in local inflammation compared with LPS in plasma. The results show that protein/peptide aggregation is a mechanism for confining LPS and reducing inflammation, further emphasizing the connection between host defense and amyloidogenesis.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bacteriology, cell biology, Immunology
in
iScience
volume
26
issue
10
article number
107951
publisher
Elsevier
external identifiers
  • pmid:37817942
  • scopus:85172402839
ISSN
2589-0042
DOI
10.1016/j.isci.2023.107951
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Author(s)
id
5f101ce7-5f44-4ac4-80f0-403a7d895752
date added to LUP
2023-12-07 15:41:26
date last changed
2024-04-20 09:56:11
@article{5f101ce7-5f44-4ac4-80f0-403a7d895752,
  abstract     = {{<p>Bacterial lipopolysaccharide (LPS) induces rapid protein aggregation in human wound fluid. We aimed to characterize these LPS-induced aggregates and their functional implications using a combination of mass spectrometry analyses, biochemical assays, biological imaging, cell experiments, and animal models. The wound-fluid aggregates encompass diverse protein classes, including sequences from coagulation factors, annexins, histones, antimicrobial proteins/peptides, and apolipoproteins. We identified proteins and peptides with a high aggregation propensity and verified selected components through Western blot analysis. Thioflavin T and Amytracker staining revealed amyloid-like aggregates formed after exposure to LPS in vitro in human wound fluid and in vivo in porcine wound models. Using NF-κB-reporter mice and IVIS bioimaging, we demonstrate that such wound-fluid LPS aggregates induce a significant reduction in local inflammation compared with LPS in plasma. The results show that protein/peptide aggregation is a mechanism for confining LPS and reducing inflammation, further emphasizing the connection between host defense and amyloidogenesis.</p>}},
  author       = {{Petrlova, Jitka and Hartman, Erik and Petruk, Ganna and Lim, Jeremy Chun Hwee and Adav, Sunil Shankar and Kjellström, Sven and Puthia, Manoj and Schmidtchen, Artur}},
  issn         = {{2589-0042}},
  keywords     = {{Bacteriology; cell biology; Immunology}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Selective protein aggregation confines and inhibits endotoxins in wounds : Linking host defense to amyloid formation}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2023.107951}},
  doi          = {{10.1016/j.isci.2023.107951}},
  volume       = {{26}},
  year         = {{2023}},
}