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- W2285571242 abstract "The dietary n-3 PUFA, eicosapentaenoic acid (EPA) is thought to be anti-inflammatory. However, data on its ability to regulate leukocyte recruitment by vascular endothelial cells (EC) is scant. Here, primary human EC were treated with EPA for 24h prior to stimulation with TNF-α and assessment of neutrophil recruitment in a flow-based assay. At levels achievable by dietary supplementation, EPA dose-dependently decreased migration of neutrophils through the EC without inhibiting their stable adhesion to the surface, a process requiring initial CXC chemokine derived signals that were unaffected by EPA. Inhibition could be replicated using inhibitors of cycloxygenase (COX-)1 and 2, while in the presence of EPA, neutrophil migration could be reconstituted by addition of arachidonic acid (AA) during the period of cytokine stimulation. These results strongly imply a role for COX generated eicosanoids in neutrophil trans-migration. Treating neutrophils with the prostaglandin-D2 [PGD2] receptor antagonist, BW868C, also dose-dependently inhibited neutrophil migration across TNF stimulated EC. Conversely, perfusion of PGD2 (derived from AA) but not PGD3 (derived from EPA) across neutrophils bound to EPA-treated EC induced them to migrate normally. Thus we describe a new PGD2-dependent step in neutrophil migration acting down stream of chemokine activation which is inhibited by EPA. Funded by the BBSRC and BHF." @default.
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- W2285571242 date "2008-04-01" @default.
- W2285571242 modified "2023-10-16" @default.
- W2285571242 title "The anti‐inflammatory effects of the n‐3PUFA, eicosapentaenoic acid, reveal a new and essential regulatory step in neutrophil migration across endothelial cells that requires prostaglandin‐D2" @default.
- W2285571242 doi "https://doi.org/10.1096/fasebj.22.2_supplement.441" @default.
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