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Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain.

Publication ,  Journal Article
Serhan, CN; Dalli, J; Karamnov, S; Choi, A; Park, C-K; Xu, Z-Z; Ji, R-R; Zhu, M; Petasis, NA
Published in: FASEB J
April 2012

Self-resolving inflammatory exudates and lipid mediator metabolomics recently uncovered a new family of potent anti-inflammatory and proresolving mediators biosynthesized by macrophages (MΦs), denoted maresins. Here we determined that maresin 1 (MaR1) produced by human MΦs from endogenous docosahexaenoic acid (DHA) matched synthetic 7R,14S-dihydroxydocosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid. The MaR1 alcohol groups and Z/E geometry of conjugated double bonds were matched using isomers prepared by total organic synthesis. MaR1's potent defining actions were confirmed with synthetic MaR1, i.e., limiting polymorphonuclear neutrophil (PMN) infiltration in murine peritonitis (ng/mouse range) as well as enhancing human macrophage uptake of apoptotic PMNs. At 1 nM, MaR1 was slightly more potent than resolvin D1 in stimulating human MΦ efferocytosis, an action not shared by leukotriene B(4). MaR1 also accelerated surgical regeneration in planaria, increasing the rate of head reappearance. On injury of planaria, MaR1 was biosynthesized from deuterium-labeled (d(5))-DHA that was blocked with lipoxygenase (LOX) inhibitor. MaR1 dose-dependently inhibited TRPV1 currents in neurons, blocked capsaicin (100 nM)-induced inward currents (IC(50) 0.49±0.02 nM), and reduced both inflammation- and chemotherapy-induced neuropathic pain in mice. These results demonstrate the potent actions of MaR1 in regulating inflammation resolution, tissue regeneration, and pain resolution. These findings suggest that chemical signals are shared in resolution cellular trafficking, a key process in tissue regeneration. Moreover, immunoresolvents of the innate immune response, such as MaR1, offer new opportunities for assessing MΦs and their local DHA metabolome in the return to tissue homeostasis.

Duke Scholars

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Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

April 2012

Volume

26

Issue

4

Start / End Page

1755 / 1765

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • TRPV Cation Channels
  • Regeneration
  • Planarians
  • Patch-Clamp Techniques
  • Pain Measurement
  • Pain
  • Neurons
  • Molecular Structure
  • Mice
 

Citation

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ICMJE
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Serhan, C. N., Dalli, J., Karamnov, S., Choi, A., Park, C.-K., Xu, Z.-Z., … Petasis, N. A. (2012). Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB J, 26(4), 1755–1765. https://doi.org/10.1096/fj.11-201442
Serhan, Charles N., Jesmond Dalli, Sergey Karamnov, Alexander Choi, Chul-Kyu Park, Zhen-Zhong Xu, Ru-Rong Ji, Min Zhu, and Nicos A. Petasis. “Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain.FASEB J 26, no. 4 (April 2012): 1755–65. https://doi.org/10.1096/fj.11-201442.
Serhan CN, Dalli J, Karamnov S, Choi A, Park C-K, Xu Z-Z, et al. Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB J. 2012 Apr;26(4):1755–65.
Serhan, Charles N., et al. “Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain.FASEB J, vol. 26, no. 4, Apr. 2012, pp. 1755–65. Pubmed, doi:10.1096/fj.11-201442.
Serhan CN, Dalli J, Karamnov S, Choi A, Park C-K, Xu Z-Z, Ji R-R, Zhu M, Petasis NA. Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB J. 2012 Apr;26(4):1755–1765.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

April 2012

Volume

26

Issue

4

Start / End Page

1755 / 1765

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • TRPV Cation Channels
  • Regeneration
  • Planarians
  • Patch-Clamp Techniques
  • Pain Measurement
  • Pain
  • Neurons
  • Molecular Structure
  • Mice