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Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions

The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the...

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Autores principales: Serhan, Charles N., Yang, Rong, Martinod, Kimberly, Kasuga, Kie, Pillai, Padmini S., Porter, Timothy F., Oh, Sungwhan F., Spite, Matthew
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626672/
https://www.ncbi.nlm.nih.gov/pubmed/19103881
http://dx.doi.org/10.1084/jem.20081880
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author Serhan, Charles N.
Yang, Rong
Martinod, Kimberly
Kasuga, Kie
Pillai, Padmini S.
Porter, Timothy F.
Oh, Sungwhan F.
Spite, Matthew
author_facet Serhan, Charles N.
Yang, Rong
Martinod, Kimberly
Kasuga, Kie
Pillai, Padmini S.
Porter, Timothy F.
Oh, Sungwhan F.
Spite, Matthew
author_sort Serhan, Charles N.
collection PubMed
description The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to activated MΦs converted these substrates to novel dihydroxy-containing products that possessed potent antiinflammatory and proresolving activity with a potency similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic acid, and protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Stable isotope incorporation, intermediate trapping, and characterization of physical and biological properties of the products demonstrated a novel 14-lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, coined MΦ mediator in resolving inflammation (maresin), which enhances resolution. These findings suggest that maresins and this new metabolome may be involved in some of the beneficial actions of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense.
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spelling pubmed-26266722009-07-19 Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions Serhan, Charles N. Yang, Rong Martinod, Kimberly Kasuga, Kie Pillai, Padmini S. Porter, Timothy F. Oh, Sungwhan F. Spite, Matthew J Exp Med Brief Definitive Reports The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to activated MΦs converted these substrates to novel dihydroxy-containing products that possessed potent antiinflammatory and proresolving activity with a potency similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic acid, and protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Stable isotope incorporation, intermediate trapping, and characterization of physical and biological properties of the products demonstrated a novel 14-lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, coined MΦ mediator in resolving inflammation (maresin), which enhances resolution. These findings suggest that maresins and this new metabolome may be involved in some of the beneficial actions of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense. The Rockefeller University Press 2009-01-19 /pmc/articles/PMC2626672/ /pubmed/19103881 http://dx.doi.org/10.1084/jem.20081880 Text en © 2009 Serhan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Reports
Serhan, Charles N.
Yang, Rong
Martinod, Kimberly
Kasuga, Kie
Pillai, Padmini S.
Porter, Timothy F.
Oh, Sungwhan F.
Spite, Matthew
Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
title Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
title_full Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
title_fullStr Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
title_full_unstemmed Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
title_short Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
title_sort maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626672/
https://www.ncbi.nlm.nih.gov/pubmed/19103881
http://dx.doi.org/10.1084/jem.20081880
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