Selective protein aggregation confines and inhibits endotoxins in wounds : Linking host defense to amyloid formation
(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.
(Less)
- author
- Petrlova, Jitka LU ; Hartman, Erik ; Petruk, Ganna LU ; Lim, Jeremy Chun Hwee LU ; Adav, Sunil Shankar ; Kjellström, Sven LU ; Puthia, Manoj LU and Schmidtchen, Artur LU
- organization
- publishing date
- 2023-10-20
- 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}}, }