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Novel n-3 immunoresolvents: structures and actions.

Dalli J, Colas RA, Serhan CN - Sci Rep (2013)

Bottom Line: The new n-3 DPA structures include 7,8,17-trihydroxy-9,11,13,15E,19Z-docosapentaenoic acid (RvD1(n-3 DPA)), 7,14-dihydroxy-8,10,12,16Z,19Z-docosapentaenoic acid (MaR1(n-3 DPA)) and related bioactive products.Each n-3 DPA-SPM displayed protective actions from second organ injury and reduced systemic inflammation in ischemia-reperfusion.Together, these findings demonstrate that n-3 DPA is converted to novel immunoresolvents with actions comparable to resolvins and are likely produced in humans when n-3 DPA is elevated.

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
Resolution of inflammation is now held to be an active process where autacoids promote homeostasis. Using functional-metabololipidomics and in vivo systems, herein we report that endogenous n-3 docosapentaenoic (DPA) acid is converted during inflammation-resolution in mice and by human leukocytes to novel n-3 products congenerous to D-series resolvins (Rv), protectins (PD) and maresins (MaR), termed specialized pro-resolving mediators (SPM). The new n-3 DPA structures include 7,8,17-trihydroxy-9,11,13,15E,19Z-docosapentaenoic acid (RvD1(n-3 DPA)), 7,14-dihydroxy-8,10,12,16Z,19Z-docosapentaenoic acid (MaR1(n-3 DPA)) and related bioactive products. Each n-3 DPA-SPM displayed protective actions from second organ injury and reduced systemic inflammation in ischemia-reperfusion. The n-3 DPA-SPM, including RvD1(n-3 DPA) and MaR1(n-3 DPA), each exerted potent leukocyte directed actions in vivo. With human leukocytes each n-3 DPA-SPM reduced neutrophil chemotaxis, adhesion and enhanced macrophage phagocytosis. Together, these findings demonstrate that n-3 DPA is converted to novel immunoresolvents with actions comparable to resolvins and are likely produced in humans when n-3 DPA is elevated.

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n-3 DPA levels increase in acute inflammation and is converted to novel products in vivo.Mice were subjected to ischemia reperfusion injury (see Methods for details) at 2 h of reperfusion, blood was collected via cardiac puncture and plasma was obtained by centrifugation, products were extracted and monohydroxy n-3 DPA levels were assessed by lipid mediator metabololipidomics. (a) Plasma polyunsaturated fatty acid levels; (b) Representative chromatographs obtained by Multiple Reaction Monitoring (MRM) of the parent ion (Q1) m/z 345 and a diagnostic daughter ion (Q3) m/z 327. (c) Monohydroxy-containing levels in plasma of sham mice and mice subjected to I/R. Results for a and c are mean ± SEM. n = 4. Results for b are representative of n = 4. *P < 0.05; **P < 0.01; ***P < 0.01 vs. sham mice.
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f2: n-3 DPA levels increase in acute inflammation and is converted to novel products in vivo.Mice were subjected to ischemia reperfusion injury (see Methods for details) at 2 h of reperfusion, blood was collected via cardiac puncture and plasma was obtained by centrifugation, products were extracted and monohydroxy n-3 DPA levels were assessed by lipid mediator metabololipidomics. (a) Plasma polyunsaturated fatty acid levels; (b) Representative chromatographs obtained by Multiple Reaction Monitoring (MRM) of the parent ion (Q1) m/z 345 and a diagnostic daughter ion (Q3) m/z 327. (c) Monohydroxy-containing levels in plasma of sham mice and mice subjected to I/R. Results for a and c are mean ± SEM. n = 4. Results for b are representative of n = 4. *P < 0.05; **P < 0.01; ***P < 0.01 vs. sham mice.

Mentions: Having found that n-3 DPA products display potent actions during ischemia reperfusion, we next investigated the role of endogenous n-3 DPA derived in the control of acute inflammation. First we assessed the plasma levels of unesterified arachidonic acid (AA), eicosapentaenoic acid (EPA), n-3 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in mice that were not subjected to an inflammatory stimulus. Plasma AA levels were 573.0 ng/ml, EPA levels were 116.2 ng/ml, n-3 DPA levels were 66.3 ng/ml and DHA levels were 146.1 ng/ml. Following ischemia reperfusion injury, circulating values for all 4 PUFA were elevated, with levels for n-3 DPA increasing ~12 times to those found in uninjured mice (Fig. 2a).


Novel n-3 immunoresolvents: structures and actions.

Dalli J, Colas RA, Serhan CN - Sci Rep (2013)

n-3 DPA levels increase in acute inflammation and is converted to novel products in vivo.Mice were subjected to ischemia reperfusion injury (see Methods for details) at 2 h of reperfusion, blood was collected via cardiac puncture and plasma was obtained by centrifugation, products were extracted and monohydroxy n-3 DPA levels were assessed by lipid mediator metabololipidomics. (a) Plasma polyunsaturated fatty acid levels; (b) Representative chromatographs obtained by Multiple Reaction Monitoring (MRM) of the parent ion (Q1) m/z 345 and a diagnostic daughter ion (Q3) m/z 327. (c) Monohydroxy-containing levels in plasma of sham mice and mice subjected to I/R. Results for a and c are mean ± SEM. n = 4. Results for b are representative of n = 4. *P < 0.05; **P < 0.01; ***P < 0.01 vs. sham mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672887&req=5

f2: n-3 DPA levels increase in acute inflammation and is converted to novel products in vivo.Mice were subjected to ischemia reperfusion injury (see Methods for details) at 2 h of reperfusion, blood was collected via cardiac puncture and plasma was obtained by centrifugation, products were extracted and monohydroxy n-3 DPA levels were assessed by lipid mediator metabololipidomics. (a) Plasma polyunsaturated fatty acid levels; (b) Representative chromatographs obtained by Multiple Reaction Monitoring (MRM) of the parent ion (Q1) m/z 345 and a diagnostic daughter ion (Q3) m/z 327. (c) Monohydroxy-containing levels in plasma of sham mice and mice subjected to I/R. Results for a and c are mean ± SEM. n = 4. Results for b are representative of n = 4. *P < 0.05; **P < 0.01; ***P < 0.01 vs. sham mice.
Mentions: Having found that n-3 DPA products display potent actions during ischemia reperfusion, we next investigated the role of endogenous n-3 DPA derived in the control of acute inflammation. First we assessed the plasma levels of unesterified arachidonic acid (AA), eicosapentaenoic acid (EPA), n-3 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in mice that were not subjected to an inflammatory stimulus. Plasma AA levels were 573.0 ng/ml, EPA levels were 116.2 ng/ml, n-3 DPA levels were 66.3 ng/ml and DHA levels were 146.1 ng/ml. Following ischemia reperfusion injury, circulating values for all 4 PUFA were elevated, with levels for n-3 DPA increasing ~12 times to those found in uninjured mice (Fig. 2a).

Bottom Line: The new n-3 DPA structures include 7,8,17-trihydroxy-9,11,13,15E,19Z-docosapentaenoic acid (RvD1(n-3 DPA)), 7,14-dihydroxy-8,10,12,16Z,19Z-docosapentaenoic acid (MaR1(n-3 DPA)) and related bioactive products.Each n-3 DPA-SPM displayed protective actions from second organ injury and reduced systemic inflammation in ischemia-reperfusion.Together, these findings demonstrate that n-3 DPA is converted to novel immunoresolvents with actions comparable to resolvins and are likely produced in humans when n-3 DPA is elevated.

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
Resolution of inflammation is now held to be an active process where autacoids promote homeostasis. Using functional-metabololipidomics and in vivo systems, herein we report that endogenous n-3 docosapentaenoic (DPA) acid is converted during inflammation-resolution in mice and by human leukocytes to novel n-3 products congenerous to D-series resolvins (Rv), protectins (PD) and maresins (MaR), termed specialized pro-resolving mediators (SPM). The new n-3 DPA structures include 7,8,17-trihydroxy-9,11,13,15E,19Z-docosapentaenoic acid (RvD1(n-3 DPA)), 7,14-dihydroxy-8,10,12,16Z,19Z-docosapentaenoic acid (MaR1(n-3 DPA)) and related bioactive products. Each n-3 DPA-SPM displayed protective actions from second organ injury and reduced systemic inflammation in ischemia-reperfusion. The n-3 DPA-SPM, including RvD1(n-3 DPA) and MaR1(n-3 DPA), each exerted potent leukocyte directed actions in vivo. With human leukocytes each n-3 DPA-SPM reduced neutrophil chemotaxis, adhesion and enhanced macrophage phagocytosis. Together, these findings demonstrate that n-3 DPA is converted to novel immunoresolvents with actions comparable to resolvins and are likely produced in humans when n-3 DPA is elevated.

Show MeSH
Related in: MedlinePlus