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• W4308372965 endingPage "1256" @default.
• W4308372965 startingPage "1250" @default.
• W4308372965 abstract "Thermal burn injuries (TBIs) in patients who are alcohol-intoxicated result in greater morbidity and mortality. The systemic toxicity found in human patients, which includes both immediate systemic cytokine generation with multiple organ failure and a delayed systemic immunosuppression, has previously been replicated in mouse models combining ethanol and localized TBI. Though considerable insights have been provided with these models, the exact mechanisms for these pathologic effects are unclear. In this review, we highlight the roles of the lipid mediator platelet-activating factor (PAF) and subcellular microvesicle particle (MVP) release in response to intoxicated thermal burn injury (ITBI) as effectors in the pathology. Particularly, MVP is released from keratinocytes in response to PAF receptor (PAFR) activation due to excess PAF produced by ITBI. These subcellular particles carry and thus protect the metabolically labile PAF which enable binding of this potent lipid mediator to several key sites. We hypothesize that PAF carried by MVP can bind to PAFR within the gut, activating myosin light chain kinase (MLCK). The subsequent gut barrier dysfunction in response to MLCK activation then allows bacteria to invade the lymphatic system and, eventually, the bloodstream, resulting in sepsis and resultant dysregulated inflammation in multiple organs. PAF in MVP also activate the skin mast cell PAFR resulting in migration of this key effector cell to the lymph nodes to induce immunosuppression. This review thus provides a mechanism and potential therapeutic approaches for the increased toxicity and immunosuppressive outcomes of TBI in the presence of acute ethanol exposure." @default.
• W4308372965 created "2022-11-11" @default.
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• W4308372965 date "2022-11-01" @default.
• W4308372965 modified "2023-10-17" @default.
• W4308372965 title "Platelet‐activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury" @default.
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• W4308372965 doi "https://doi.org/10.1002/biof.1917" @default.
• W4308372965 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36342751" @default.
• W4308372965 hasPublicationYear "2022" @default.
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