Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation
Summary: 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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422302028X |
| _version_ | 1797647796219674624 |
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| author | Jitka Petrlova Erik Hartman Ganna Petruk Jeremy Chun Hwee Lim Sunil Shankar Adav Sven Kjellström Manoj Puthia Artur Schmidtchen |
| author_facet | Jitka Petrlova Erik Hartman Ganna Petruk Jeremy Chun Hwee Lim Sunil Shankar Adav Sven Kjellström Manoj Puthia Artur Schmidtchen |
| author_sort | Jitka Petrlova |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-11T15:21:41Z |
| format | Article |
| id | doaj.art-02dcad32e1ee44f1bdf6cafc2d37d0a9 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:21:41Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-02dcad32e1ee44f1bdf6cafc2d37d0a92023-10-28T05:09:06ZengElsevieriScience2589-00422023-10-012610107951Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formationJitka Petrlova0Erik Hartman1Ganna Petruk2Jeremy Chun Hwee Lim3Sunil Shankar Adav4Sven Kjellström5Manoj Puthia6Artur Schmidtchen7Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, Sweden; Corresponding authorDivision of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, SwedenDivision of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, SwedenDivision of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, SwedenSchool of Materials Science and Engineering, Nanyang Technological University, Singapore, SingaporeDepartment of Clinical Sciences, BioMS, Lund University, Lund, SwedenDivision of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, SwedenDivision of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, Sweden; Dermatology, Skane University Hospital, 22185 Lund, SwedenSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422302028XImmunologyBacteriologycell biology |
| spellingShingle | Jitka Petrlova Erik Hartman Ganna Petruk Jeremy Chun Hwee Lim Sunil Shankar Adav Sven Kjellström Manoj Puthia Artur Schmidtchen Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation iScience Immunology Bacteriology cell biology |
| title | Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation |
| title_full | Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation |
| title_fullStr | Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation |
| title_full_unstemmed | Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation |
| title_short | Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation |
| title_sort | selective protein aggregation confines and inhibits endotoxins in wounds linking host defense to amyloid formation |
| topic | Immunology Bacteriology cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422302028X |
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