DOI: 10.1084/jem.20020760. Resolvins

Resolvins

10.1084/jem.20020760

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R-containing precursors of endogenous antiinflammatory mediators. Here, we report that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family of bioactive 17R-hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17R-hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17R-HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA–derived 17R-hydroxy-DHA into two sets of novel di- and trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC50 ∼50 pM) microglial cell cytokine expression and in vivo dermal inflammation and peritonitis at ng doses, reducing 40–80% leukocytic exudates. These results indicate that exudates, vascular, leukocytes and neural cells treated with aspirin convert DHA to novel 17R-hydroxy series of docosanoids that are potent regulators. These biosynthetic pathways utilize omega-3 DHA and EPA during multicellular events in resolution to produce a family of protective compounds, i.e., resolvins, that enhance proresolution status.

Bibliography

Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G., & Moussignac, R.-L. (2002). Resolvins. The Journal of Experimental Medicine, 196(8), 1025â1037.

Authors 7

Charles N. Serhan (first)
Song Hong (additional)
Karsten Gronert (additional)
Sean P. Colgan (additional)
Pallavi R. Devchand (additional)
Gudrun Mirick (additional)
Rose-Laure Moussignac (additional)

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Dates

Type	When
Created	22 years, 10 months ago (Oct. 21, 2002, 3:24 p.m.)
Deposited	1 year, 7 months ago (Jan. 7, 2024, 10:23 a.m.)
Indexed	2 days, 17 hours ago (Sept. 3, 2025, 7:09 a.m.)
Issued	22 years, 10 months ago (Oct. 21, 2002)
Published	22 years, 10 months ago (Oct. 21, 2002)
Published Online	22 years, 10 months ago (Oct. 21, 2002)
Published Print	22 years, 10 months ago (Oct. 21, 2002)

Funders 0

None

BibTeX

@article{Serhan_2002, title={Resolvins}, volume={196}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20020760}, DOI={10.1084/jem.20020760}, number={8}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Serhan, Charles N. and Hong, Song and Gronert, Karsten and Colgan, Sean P. and Devchand, Pallavi R. and Mirick, Gudrun and Moussignac, Rose-Laure}, year={2002}, month=oct, pages={1025–1037} }

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