Skip to main content

Cell-Cell Interaction in the Transcellular Biosynthesis of Novel ω-3-Derived Lipid Mediators

  • Protocol
Cell-Cell Interactions

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 341))

Abstract

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) display beneficial actions in human diseases. The molecular basis for these actions remains of interest. We recently identified novel mediators generated from ω-3 PUFA during Cell-Cell interactions that displayed potent anti-inflammatory and proresolving actions. Compounds derived from EPA are designated resolvins of the E series (RvE1), and those biosynthesized from DHA are denoted resolvins of the D series (RvD) and docosatriene, such as protectin D1 (PD1), which belongs to the family of protectins. In addition, treatment using aspirin initiates a related epimeric series by triggering endogenous formation of the 17R-RvD series, denoted as aspirin-triggered (AT)-RvDs. These compounds possess potent anti-inflammatory actions in vivo that essentially are equivalent to their counterpart generated without aspirin, namely the 17S-RvDs. In this chapter, we provide an overview and detail protocols of the biosynthesis and bioactions of these newly uncovered pathways and products that include three distinct series: 18Rresolvins of the E series derived from EPA (i.e., RvE1); 17R-resolvins of the D series from DHA (AT-RvD1 through RvD4); and 17S-resolvins of the D series from DHA (RvD1 through RvD4).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Helgadottir, A., Manolescu, A., Thorleifsson, G., et al. (2004) The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat. Genet. 36, 233–239.

    Article  CAS  PubMed  Google Scholar 

  2. Erlinger, T. P., Platz, E. A., Rifai, N., and Helzlsouer, K. J. (2004) C-reactive protein and the risk of incident colorectal cancer. JAMA 291, 585–590.

    Article  CAS  PubMed  Google Scholar 

  3. Pasche, B. and Serhan, C. N. (2004) Is C-reactive protein an inflammation opsonin that signals colon cancer risk? JAMA 291, 623–624.

    Article  CAS  PubMed  Google Scholar 

  4. Gallin, J. I., Snydermanm, R., Fearon, D. T., Haynes, B. F., and Nathan, C. (eds.) (1999) Inflammation: Basic Principles and Clinical Correlates. Lippincott Williams & Wilkins Philadelphia.

    Google Scholar 

  5. Van Dyke, T. E. and Serhan, C. N. (2003) Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J. Dent. Res. 82, 82–90.

    Article  CAS  PubMed  Google Scholar 

  6. Burr, G. O. and Burr, M. M. (1929) A new deficiency disease produced by the rigid exclusion of fat from the diet. J. Biol. Chem. 82, 345–367.

    CAS  Google Scholar 

  7. Lands, W. E. M. (ed.) (1987) Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids. American Oil Chemists’ Society, Champaign, IL.

    Google Scholar 

  8. Bazan, N. G. (1990) Supply of n-3 polyunsaturated fatty acids and their significance in the central nervous system, in Nutrition and the Brain (Wurtman, R. J. and Wurtman, J. J., eds.), Vol. 8, Raven Press New York, pp. 1–22.

    Google Scholar 

  9. Simopoulos, A. P., Leaf, A., and Salem, N., Jr. (1999) Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. J. Am. Coll. Nutr. 18, 487–489.

    CAS  PubMed  Google Scholar 

  10. Salem, N., Jr., Litman, B., Kim, H.-Y., and Gawrisch, K. (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 36, 945–959.

    Article  CAS  PubMed  Google Scholar 

  11. Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med. 192, 1197–1204.

    Article  CAS  PubMed  Google Scholar 

  12. Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G., and Moussignac, R.-L. (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter pro-inflammation signals. J. Exp. Med. 196, 1025–1037.

    Article  CAS  PubMed  Google Scholar 

  13. Hong, S., Gronert, K., Devchand, P., Moussignac, R.-L., and Serhan, C. N. (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: autacoids in anti-inflammation. J. Biol. Chem. 278, 14,677–14,687.

    Article  CAS  PubMed  Google Scholar 

  14. Marcheselli, V. L., Hong, S., Lukiw, W. J., et al. (2003) Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J. Biol. Chem. 278, 43,807–43,817.

    Article  CAS  PubMed  Google Scholar 

  15. Mukherjee, P. K., Marcheselli, V. L., Serhan, C. N., and Bazan N. G. (2004) Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc. Natl. Acad. Sci. USA 101, 8491–8496.

    Article  CAS  PubMed  Google Scholar 

  16. Lehr, H.-A., Olofsson, A. M., Carew, T. E., et al. (1994) P-selectin mediates the interaction of circulating leukocytes with platelets and microvascular endothelium in response to oxidized lipoprotein in vivo. Lab. Invest. 71, 380–386.

    CAS  PubMed  Google Scholar 

  17. Mora, J. R., Bono, M. R., Manjunath, N., et al. (2003) Selective imprinting of guthoming T cells by Peyer’s patch dendritic cells. Nature 424, 88–93.

    Article  CAS  PubMed  Google Scholar 

  18. Serhan, C. N., Hamberg, M., and Samuelsson, B. (1984) Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc. Natl. Acad. Sci. USA 81, 5335–5339.

    Article  CAS  PubMed  Google Scholar 

  19. Serhan, C. N. and Sheppard K. A. (1990) Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro. J. Clin. Invest. 85, 772–780.

    Article  CAS  PubMed  Google Scholar 

  20. Marcus, A. J. (1999) Platelets: their role in hemostasis, thrombosis, and inflammation, in Inflammation: Basic Principles and Clinical Correlates (Gallin, J. I. and Snyderman, R.,eds.), Lippincott Williams &ampt: Wilkins Philadelphia, pp. 77–95.

    Google Scholar 

  21. Maddox, J. F. and Serhan, C. N. (1996) Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction. J. Exp. Med. 183, 137–146.

    Article  CAS  PubMed  Google Scholar 

  22. Godson, C., Mitchell, S., Harvey, K., Petasis, N. A., Hogg, N., and Brady, H. R. (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J. Immunol. 164, 1663–1667.

    CAS  PubMed  Google Scholar 

  23. Clária, J. and Serhan, C. N. (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc. Natl. Acad. Sci. USA 92, 9475–9479.

    Article  PubMed  Google Scholar 

  24. Perretti, M., Chiang, N., La, M., Fierro, I. M., Marullo, S., Getting, S. J., Solito, E., and Serhan C. N. (2002) Endogenous lipid-and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A(4) receptor. Nat. Med. 8, 1296–1302.

    Article  CAS  PubMed  Google Scholar 

  25. Vane, J. R. (2002) Back to an aspirin a day? Science 296, 474–475.

    Article  CAS  PubMed  Google Scholar 

  26. Cheng, Y., Austin, S. C., Rocca, B., et al. (2002) Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 296, 539–541.

    Article  CAS  PubMed  Google Scholar 

  27. Fierro, I. M., Colgan, S. P., Bernasconi, G., Petasis, N. A., Clish, C. B., Arita, M., et al. (2003) Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit human neutrophil migration: comparisons between synthetic 15 epimers in chemotaxis and transmigration with microvessel endothelial cells and epithelial cells. J. Immunol. 170, 2688–2694.

    CAS  PubMed  Google Scholar 

  28. Fierro, I. M., Kutok, J. L., and Serhan, C. N. (2002) Novel lipid mediator regulators of endothelial cell proliferation and migration: Aspirin-triggered-15R-lipoxin A4 and lipoxin A4. J. Pharmacol. Exp. Ther. 300, 385–392.

    Article  CAS  PubMed  Google Scholar 

  29. Kieran, N. E., Doran, P. P., Connolly, S. B., et al. (2003) Modification of the transcriptomic response to renal ischemia/reperfusion injury by lipoxin analog. Kidney Int. 64, 480–492.

    Article  CAS  PubMed  Google Scholar 

  30. Fiore, S., Ryeom, S. W., Weller, P. F., and Serhan, C. N. (1992) Lipoxin recognition sites. Specific binding of labeled lipoxin A4] with human neutrophils. J. Biol. Chem. 267, 16,168–16,176.

    CAS  PubMed  Google Scholar 

  31. Fiore, S., Maddox, J. F., Perez, H. D., and Serhan, C. N. (1994) Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J. Exp. Med. 180, 253–260.

    Article  CAS  PubMed  Google Scholar 

  32. Bae, Y.-S., Park, J. C., He, R., et al. (2003) Differential signaling of formyl peptide receptor-like 1 by Trp-Lys-Tyr-Met-Val-Met-CONH2 or lipoxin A4 in human neutrophils. Mol. Pharmacol. 63, 721–730.

    Article  Google Scholar 

  33. Gewirtz, A. T., Collier-Hyams, L. S., Young, A. N., et al. (2002) Lipoxin A4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J. Immunol. 168, 5260–5267.

    CAS  PubMed  Google Scholar 

  34. Devchand, P. R., Arita, M., Hong, S., et al (2003) Human ALX receptor regulates neutrophil recruitment in transgenic mice: Roles in inflammation and host-defense. FASEB J. 17, 652–659.

    Article  CAS  PubMed  Google Scholar 

  35. Serhan, C. N., Jain, A., Marleau, S., et al. (2003) Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous antiinflammatory lipid mediators. J. Immunol. 171, 6856–6865.

    CAS  PubMed  Google Scholar 

  36. Weissmann, G., Smolen, J. E., and Korchak, H. M. (1980) Release of inflammatory mediators from stimulated neutrophils. N. Engl. J. Med. 303, 27–34.

    Article  CAS  PubMed  Google Scholar 

  37. Samuelsson, B. (1982) From studies of biochemical mechanisms to novel biological mediators: prostaglandin endoperoxides, thromboxanes and leukotrienes, in Les Prix Nobel: Nobel Prizes, Presentations, Biographies and Lectures, Almqvist &amp: Wiksell Stockholm, pp. 153–174.

    Google Scholar 

  38. Vane, J. R. (1982) Adventures and excursions in bioassay: the stepping stones to prostacyclin, in Les Prix Nobel: Nobel Prizes, Presentations, Biographies and Lectures, Almqvist &amp: Wiksell Stockholm, pp. 181–206.

    Google Scholar 

  39. GISSI-Prevenzione Investigators (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSIPrevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 354, 447–455.

    Article  Google Scholar 

  40. Marchioli, R., Barzi, F., Bomba, E., et al. (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation 105, 1897–1903.

    Article  CAS  PubMed  Google Scholar 

  41. Rosenstein, E. D., Kushner, L. J., Kramer, N., and Kazandjian, G. (2003) Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukot. Essent. Fatty Acids 68, 213–218.

    Article  CAS  PubMed  Google Scholar 

  42. Bazan, N. G. (1992) Supply, uptake, and utilization of docosahexaenoic acid during photoreceptor cell differentiation. Nestle Nutrition Workshop Series 28, 121–133.

    CAS  Google Scholar 

  43. Lee, T. H., Mencia-Huerta, J.-M., Shih, C., Corey, E. J., Lewis, R. A., and Austen, K. F. (1984) Effects of exogenous arachidonic, eicosapentaenoic, and docosahexaenoic acids on the generation of 5-lipoxygenase pathway products by ionophore-activated human neutrophils. J. Clin. Invest. 74, 1922–1933.

    Article  CAS  PubMed  Google Scholar 

  44. Sawazaki, S., Salem, N,.Jr., and Kim H.-Y. (1994) Lipoxygenation of docosahexaenoic acid by the rat pineal body. J. Neurochem. 62, 2437–2447.

    Article  CAS  PubMed  Google Scholar 

  45. Reich, E. E., Zackert, W. E., Brame, C. J., et al. (2000) Formation of novel D-ring and E-ring isoprostane-like compounds (D4/E4-neuroprostanes) in vivo from docosahexaenoic acid. Biochemistry 39, 2376–2383.

    Article  CAS  PubMed  Google Scholar 

  46. VanRollins, M., Baker, R. C., Sprecher, H. W., and Murphy R. C. (1984) Oxidation of docosahexaenoic acid by rat liver microsomes. J. Biol. Chem. 259, 5776–5783.

    CAS  PubMed  Google Scholar 

  47. Lands, W. E. M. (2003) Diets could prevent many diseases. Lipids 38, 317–321.

    Article  CAS  PubMed  Google Scholar 

  48. Winyard, P. G. and Willoughby, D. A. (eds.) (2003) Inflammation Protocols. Humana Totowa, NJ.

    Google Scholar 

  49. Lu, Y., Hong, S., Tjonahen, E., and Serhan, C. N. (2003) Lipid mediator lipidomics: databases and search algorithms of electric spray ionization/tandem mass and ultraviolet spectra for structural elucidation, in 5th Winter Eicosanoid Conference, Baltimore.

    Google Scholar 

  50. Arita, M., Bianchini, F., Aliberti, J., et al. (2005) Stereochemical assignment, anti-inflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J. Exp. Med., 201, 713–722.

    Article  CAS  PubMed  Google Scholar 

  51. Corey, E. J., Shih, C., and Cashman, J. R. (1983) Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. Proc. Natl. Acad. Sci. USA 80, 3581–3584.

    Article  CAS  PubMed  Google Scholar 

  52. Serhan, C. N. and Oliw, E. (2001) Unorthodox routes to prostanoid formation: new twists in cyclooxygenase-initiated pathways. J. Clin. Invest. 107, 1481–1489.

    Article  CAS  PubMed  Google Scholar 

  53. Serhan, C. N., Gotlinger, K., Hong, S., et al. (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J. Immunol. 176, 1848–1859.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc.

About this protocol

Cite this protocol

Chiang, N., Serhan, C.N. (2006). Cell-Cell Interaction in the Transcellular Biosynthesis of Novel ω-3-Derived Lipid Mediators. In: Colgan, S.P. (eds) Cell-Cell Interactions. Methods in Molecular Biology™, vol 341. Humana Press. https://doi.org/10.1385/1-59745-113-4:227

Download citation

  • DOI: https://doi.org/10.1385/1-59745-113-4:227

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-523-1

  • Online ISBN: 978-1-59745-113-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics