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Vagus nerve controls resolution and pro-resolving mediators of inflammation.

Mirakaj V, Dalli J, Granja T, Rosenberger P, Serhan CN - J. Exp. Med. (2014)

Bottom Line: In netrin-1(+/-) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+).Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins.Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other's expression and enhanced efferocytosis.

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Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard-Karls University, 72076 Tübingen, Germany.

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Vagotomy shifts exudate lipid mediator profile to proinflammatory. Mice were subjected to right-sided cervical vagotomy or sham surgery and then challenged with 1 mg zymosan. Peritoneal exudates were collected at the indicated intervals and lipid mediator profiles determined by lipid mediator metabololipidomics (see Materials and methods). (A) MRM chromatograms for the identified lipid mediators in murine exudates. a and b denote LTB4 isomers: a = Δ6-trans-LTB4; b = 12-epi-Δ6-trans-LTB4. (B) Accompanying MS/MS spectra used for identification. (C) Levels of D-series resolvins, protectins, and maresins, lipoxins, and leukotriene B4, prostaglandin, and thromboxane measured at the indicated time points. Pie charts show the relative contribution of lipid mediators. Blue shading denotes proresolving and red shading denotes pro-inflammatory Results are expressed as mean ± SEM; n = 4 mice per time point for two independent experiments. *, P < 0.05; **, P < 0.01 versus inflammation mice at the respective interval.
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fig2: Vagotomy shifts exudate lipid mediator profile to proinflammatory. Mice were subjected to right-sided cervical vagotomy or sham surgery and then challenged with 1 mg zymosan. Peritoneal exudates were collected at the indicated intervals and lipid mediator profiles determined by lipid mediator metabololipidomics (see Materials and methods). (A) MRM chromatograms for the identified lipid mediators in murine exudates. a and b denote LTB4 isomers: a = Δ6-trans-LTB4; b = 12-epi-Δ6-trans-LTB4. (B) Accompanying MS/MS spectra used for identification. (C) Levels of D-series resolvins, protectins, and maresins, lipoxins, and leukotriene B4, prostaglandin, and thromboxane measured at the indicated time points. Pie charts show the relative contribution of lipid mediators. Blue shading denotes proresolving and red shading denotes pro-inflammatory Results are expressed as mean ± SEM; n = 4 mice per time point for two independent experiments. *, P < 0.05; **, P < 0.01 versus inflammation mice at the respective interval.

Mentions: Vagotomy shifted the profile of lipid mediators to increase the proinflammatory mediators, i.e., leukotriene B4 (Fig. 2), and decrease the pro-resolving mediators such as RvD1 in exudates. Each mediator was identified using LC-MS-MS–based metabololipidomics and signature diagnostic ions (Fig. 2). Within exudates, pro-resolving mediators are present, e.g., RvD1, LXA4, and PD1 (Fig. 2 B). These were sharply reduced in exudates from vagotomized mice throughout the time course (Fig. 2 C and Table 1). These exudates normally resolve by 24 h, as observed in sham-operated control mice (Fig. 2 C inset and Table S1).


Vagus nerve controls resolution and pro-resolving mediators of inflammation.

Mirakaj V, Dalli J, Granja T, Rosenberger P, Serhan CN - J. Exp. Med. (2014)

Vagotomy shifts exudate lipid mediator profile to proinflammatory. Mice were subjected to right-sided cervical vagotomy or sham surgery and then challenged with 1 mg zymosan. Peritoneal exudates were collected at the indicated intervals and lipid mediator profiles determined by lipid mediator metabololipidomics (see Materials and methods). (A) MRM chromatograms for the identified lipid mediators in murine exudates. a and b denote LTB4 isomers: a = Δ6-trans-LTB4; b = 12-epi-Δ6-trans-LTB4. (B) Accompanying MS/MS spectra used for identification. (C) Levels of D-series resolvins, protectins, and maresins, lipoxins, and leukotriene B4, prostaglandin, and thromboxane measured at the indicated time points. Pie charts show the relative contribution of lipid mediators. Blue shading denotes proresolving and red shading denotes pro-inflammatory Results are expressed as mean ± SEM; n = 4 mice per time point for two independent experiments. *, P < 0.05; **, P < 0.01 versus inflammation mice at the respective interval.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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fig2: Vagotomy shifts exudate lipid mediator profile to proinflammatory. Mice were subjected to right-sided cervical vagotomy or sham surgery and then challenged with 1 mg zymosan. Peritoneal exudates were collected at the indicated intervals and lipid mediator profiles determined by lipid mediator metabololipidomics (see Materials and methods). (A) MRM chromatograms for the identified lipid mediators in murine exudates. a and b denote LTB4 isomers: a = Δ6-trans-LTB4; b = 12-epi-Δ6-trans-LTB4. (B) Accompanying MS/MS spectra used for identification. (C) Levels of D-series resolvins, protectins, and maresins, lipoxins, and leukotriene B4, prostaglandin, and thromboxane measured at the indicated time points. Pie charts show the relative contribution of lipid mediators. Blue shading denotes proresolving and red shading denotes pro-inflammatory Results are expressed as mean ± SEM; n = 4 mice per time point for two independent experiments. *, P < 0.05; **, P < 0.01 versus inflammation mice at the respective interval.
Mentions: Vagotomy shifted the profile of lipid mediators to increase the proinflammatory mediators, i.e., leukotriene B4 (Fig. 2), and decrease the pro-resolving mediators such as RvD1 in exudates. Each mediator was identified using LC-MS-MS–based metabololipidomics and signature diagnostic ions (Fig. 2). Within exudates, pro-resolving mediators are present, e.g., RvD1, LXA4, and PD1 (Fig. 2 B). These were sharply reduced in exudates from vagotomized mice throughout the time course (Fig. 2 C and Table 1). These exudates normally resolve by 24 h, as observed in sham-operated control mice (Fig. 2 C inset and Table S1).

Bottom Line: In netrin-1(+/-) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+).Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins.Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other's expression and enhanced efferocytosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard-Karls University, 72076 Tübingen, Germany.

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Related in: MedlinePlus