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
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
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- 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.
eicosapentaenoic acid, acid
Yates, Clara
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Tull, Samantha
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Madden, Jacki
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Calder, Philip
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Grimble, Robert
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Nash, Gerard
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Rainger, Ed
d22f6d2f-f7ce-4aba-9b29-1d78cc82f985
April 2008
Yates, Clara
efdb3e6e-630f-4152-b99d-7f88a789fa91
Tull, Samantha
c7ed1edf-8826-49a1-a975-2d15af9b0fb5
Madden, Jacki
0771e352-d432-41ea-8a7e-4704c1efca46
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Grimble, Robert
3100e4d2-8f29-4ca6-a95d-38a6a764865f
Nash, Gerard
f227974f-baf4-4f4a-9891-01ccb0dcf937
Rainger, Ed
d22f6d2f-f7ce-4aba-9b29-1d78cc82f985
Yates, Clara, Tull, Samantha, Madden, Jacki, Calder, Philip, Grimble, Robert, Nash, Gerard and Rainger, Ed
(2008)
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.
FASEB Journal, 22.
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- 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.
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Published date: April 2008
Keywords:
eicosapentaenoic acid, acid
Organisations:
Medicine
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Local EPrints ID: 70587
URI: http://eprints.soton.ac.uk/id/eprint/70587
ISSN: 0892-6638
PURE UUID: 5d266ef8-2200-4fc0-ad19-07ddc15dd029
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Date deposited: 10 Mar 2010
Last modified: 11 Dec 2021 03:09
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Contributors
Author:
Clara Yates
Author:
Samantha Tull
Author:
Jacki Madden
Author:
Robert Grimble
Author:
Gerard Nash
Author:
Ed Rainger
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