Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis
Abstract Background Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide o...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-023-01301-5 |
| _version_ | 1797577289934831616 |
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| author | Min Wang Jun Feng Daixing Zhou Junshuai Wang |
| author_facet | Min Wang Jun Feng Daixing Zhou Junshuai Wang |
| author_sort | Min Wang |
| collection | DOAJ |
| description | Abstract Background Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis. Main findings LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics. Conclusions To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis. Graphical Abstract |
| first_indexed | 2024-03-10T22:06:08Z |
| format | Article |
| id | doaj.art-300f1b623f7048d695d4d7b850d945bc |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-10T22:06:08Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-300f1b623f7048d695d4d7b850d945bc2023-11-19T12:47:17ZengBMCEuropean Journal of Medical Research2047-783X2023-09-0128111610.1186/s40001-023-01301-5Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsisMin Wang0Jun Feng1Daixing Zhou2Junshuai Wang3Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis. Main findings LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics. Conclusions To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis. Graphical Abstracthttps://doi.org/10.1186/s40001-023-01301-5LipopolysaccharideTLR4Endothelial cellsSepsis |
| spellingShingle | Min Wang Jun Feng Daixing Zhou Junshuai Wang Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis European Journal of Medical Research Lipopolysaccharide TLR4 Endothelial cells Sepsis |
| title | Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis |
| title_full | Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis |
| title_fullStr | Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis |
| title_full_unstemmed | Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis |
| title_short | Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis |
| title_sort | bacterial lipopolysaccharide induced endothelial activation and dysfunction a new predictive and therapeutic paradigm for sepsis |
| topic | Lipopolysaccharide TLR4 Endothelial cells Sepsis |
| url | https://doi.org/10.1186/s40001-023-01301-5 |
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