AI Article Synopsis
- Modulating SYK can influence how neutrophils respond in COVID-19 and sepsis, where they can both protect against infections and contribute to tissue damage during hyperactivation.
- R406, a metabolite of fostamatinib, effectively inhibits key harmful neutrophil activities like NETosis and ROS generation, which are associated with severe sepsis outcomes.
- Despite these inhibitory effects, neutrophils treated with R406 remain metabolically active and can still perform essential functions like cytokine release, phagocytosis, and migration.
Article Abstract
Modulating SYK has been demonstrated to have impacts on pathogenic neutrophil responses in COVID-19. During sepsis, neutrophils are vital in early bacterial clearance but also contribute to the dysregulated immune response and organ injury when hyperactivated. Here, we evaluated the impact of R406, the active metabolite of fostamatinib, on neutrophils stimulated by LPS. We demonstrate that R406 was able to effectively inhibit NETosis, degranulation, ROS generation, neutrophil adhesion, and the formation of CD16 neutrophils that have been linked to detrimental outcomes in severe sepsis. Further, the neutrophils remain metabolically active, capable of releasing cytokines, perform phagocytosis, and migrate in response to IL-8. Taken together, this data provides evidence of the potential efficacy of utilizing fostamatinib in bacterial sepsis.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387147 | PMC |
| http://dx.doi.org/10.1016/j.cellimm.2024.104860 | DOI Listing |
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