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. 2006 Apr 28;8(2):E284–E297. doi: 10.1007/BF02854899

Lipid mediator informatics-lipidomics: Novel pathways in mapping resolution

Charles N Serhan 1,✉, Song Hong 1, Yan Lu 1
PMCID: PMC3231579  PMID: 16796379

Abstract

Lipidomics, the systematic decoding of lipid-based information in biosystems, is composed of identifying and profiling lipids and lipid-derived mediators. As currently practiced, lipidomics can be subdivided into architecture/ membrane lipidomics and mediator lipidomics. The mapping of structural components and their relation to cell activation as well as generation of potent lipid mediators and networks involves a mass spectrometry-computational approach so that interrelationships and complex mediator networks important for cell homeostasis can be appreciated. Cell membranes are composed of a bilayer that contains phospholipids, fatty acids, integral membrane proteins, membrane-associated proteins, sphingolipids, and so on. The membrane composition of many cell types has been established. The components' organization and effect on cell function remains to be established, however, and is a quest for lipidomics. Here, we review liquid chromatography tandem mass spectrometry-based lipidomic analyses to address bioactive lipid mediators in signaling pathways and the roles of lipid-derived mediators in resolution of inflammation.

Keywords: Mediators, eicosanoids, ω-3 essential fatty acids, inflammation

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References

  • 1.Samuelsson B, Dahlén SE, Lindgren JÅ, Rouzer CA, Serhan CN. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987;237:1171–1176. doi: 10.1126/science.2820055. [DOI] [PubMed] [Google Scholar]
  • 2.Bergström S, The Nobel Foundation . Les Prix Nobel: Nobel Prizes, Presentations, Biographies and Lectures. Stockholm, Sweden: Almqvist & Wiksell; 1982. The prostaglandins: from the laboratory to the clinic; pp. 129–148. [Google Scholar]
  • 3.Lu Y, Hong S, Tjonahen E, Serhan CN. Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators. J Lipid Res. 2005;46:790–802. doi: 10.1194/jlr.D400020-JLR200. [DOI] [PubMed] [Google Scholar]
  • 4.Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K. 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. 2000;192:1197–1204. doi: 10.1084/jem.192.8.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Hannun YA, Obeid LM. The ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J Biol Chem. 2002;277:25847–25850. doi: 10.1074/jbc.R200008200. [DOI] [PubMed] [Google Scholar]
  • 6.Gronert K, Kantarci A, Levy BD, et al. A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage. J Immunol. 2004;172:1856–1861. doi: 10.4049/jimmunol.172.3.1856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Serhan CN, Jain A, Marleau S, et al. Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J Immunol. 2003;171:6856–6865. doi: 10.4049/jimmunol.171.12.6856. [DOI] [PubMed] [Google Scholar]
  • 8.Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol. 2001;2:612–619. doi: 10.1038/89759. [DOI] [PubMed] [Google Scholar]
  • 9.Serhan CN, Hong S, Gronert K, et al. 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. 2002;196:1025–1037. doi: 10.1084/jem.20020760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Calder PC. Polyunsaturated fatty acids inflammation, and immunity. Lipids. 2001;36:1007–1024. doi: 10.1007/s11745-001-0812-7. [DOI] [PubMed] [Google Scholar]
  • 11.Serhan CN. Mediator lipidomics. Prostaglandins Other Lipid Mediat. 2005;77:4–14. doi: 10.1016/j.prostaglandins.2004.09.016. [DOI] [PubMed] [Google Scholar]
  • 12.Serhan CN, Gotlinger K, Hong S, Arita M. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat. 2004;73:155–172. doi: 10.1016/j.prostaglandins.2004.03.005. [DOI] [PubMed] [Google Scholar]
  • 13.Murphy RC, Fiedler J, Hevko J. Analysis of nonvolatile lipids by mass spectrometry. Chem Rev. 2001;101:479–526. doi: 10.1021/cr9900883. [DOI] [PubMed] [Google Scholar]
  • 14.Ausloos P, Clifton CL, Lias SG, et al. The critical evaluation of a comprehensive mass spectral library. J Am Soc Mass Spectrom. 1999;10:287–299. doi: 10.1016/S1044-0305(98)00159-7. [DOI] [PubMed] [Google Scholar]
  • 15.Stein SE. Chemical substructure identification by mass spectral library searching. J Am Soc Mass Spectrom. 1995;6:644–655. doi: 10.1016/1044-0305(95)00291-K. [DOI] [PubMed] [Google Scholar]
  • 16.Stein SE, Scott DR. Optimization and testing of mass spectral library search algorithms for compound identification. J Am Soc Mass Spectrom. 1994;5:859–866. doi: 10.1016/1044-0305(94)87009-8. [DOI] [PubMed] [Google Scholar]
  • 17.Mallard GW, Reed J. Automated Mass Spectral Deconvolution & Identification Systems. Gaithersburg: MDUS Department of Commerce—Technology Administration, National Institutes of Standards and Technology Standard Reference Data Program; 1997. [Google Scholar]
  • 18.Chiang N, Takano T, Clish CB, Petasis NA, Tai H-H, Serhan CN. Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA. J Pharmacol Exp Ther. 1998;287:779–790. [PubMed] [Google Scholar]
  • 19.Griffiths WJ, Yang Y, Sjövall J, Lindgren JÅ. Electrospray/collision-induced dissociation mass spectrometry of mono-, di- and tri-hydroxylated lipoxygenase products, including leukotrienes of the B-series and lipoxins. Rapid Commun Mass Spectrom. 1996;10:183–196. doi: 10.1002/(SICI)1097-0231(19960131)10:2<183::AID-RCM456>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  • 20.Hong S, Gronert K, Devchand P, Moussignac R-L, Serhan CN. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: autacoids in anti-inflammation. J Biol Chem. 2003;278:14677–14687. doi: 10.1074/jbc.M300218200. [DOI] [PubMed] [Google Scholar]
  • 21.Wenk MR, Lucast L, Paolo GD, et al. Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry. Nat Biotechnol. 2003;21:813–817. doi: 10.1038/nbt837. [DOI] [PubMed] [Google Scholar]
  • 22.Serhan CN. On the relationship between leukotriene and lipoxin production by human neutrophils: evidence for differential metabolism of 15-HETE and 5-HETE. Biochim Biophys Acta. 1989;1004:158–168. doi: 10.1016/0005-2760(89)90264-6. [DOI] [PubMed] [Google Scholar]
  • 23.Kiss L, Bieniek E, Weissmann N, et al. Simultaneous analysis of 4- and 5-series lipoxygenase and cytochrome P450 products from different biological sources by reversed-phase high-performance liquid chromatographic technique. Anal. Biochem. 1998;261:16–28. doi: 10.1006/abio.1998.2674. [DOI] [PubMed] [Google Scholar]
  • 24.Aliberti J, Hieny S, Reis e Sousa C, Serhan CN, Sher A. Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity. Nat Immunol. 2002;3:76–82. doi: 10.1038/ni745. [DOI] [PubMed] [Google Scholar]
  • 25.McLafferty FW, Turecek F. Elemental composition. In: Imfeld I, Kelly A, editors. Interpretation of Mass Spectra. 4th ed. Mill Valley, CA: University Science Books; 1993. pp. 19–34. [Google Scholar]
  • 26.Wan KX, Vidavsky I, Gross ML. Comparing similar spectra: from similarity index to spectral contrast angle. J Am Soc Mass Spectrom. 2002;13:85–88. doi: 10.1016/S1044-0305(01)00327-0. [DOI] [PubMed] [Google Scholar]
  • 27.User Manual LCQTM. San Jose, CA: Finnigan MAT, 1996.
  • 28.McLafferty FW, Stauffer DA, Loh Y, Wesdemiotis C. Unknown identification using reference mass spectra: quality evaluation of databases. J Am Soc Mass Spectrom. 1999;10:1229–1240. doi: 10.1016/S1044-0305(99)00104-X. [DOI] [PubMed] [Google Scholar]
  • 29.Wheelan PJ, Zirrolli JA, Murphy RC. Electrospray ionization and low energy tandem mass spectrometry of polyhydroxy unsaturated fatty acids. J Am Soc Mass Spectrom. 1996;7:140–149. doi: 10.1016/1044-0305(95)00628-1. [DOI] [PubMed] [Google Scholar]
  • 30.Salem N, Litman B, Kim H-Y, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001;36:945–959. doi: 10.1007/s11745-001-0805-6. [DOI] [PubMed] [Google Scholar]
  • 31.Serhan CN, Gotlinger K, Hong S, et al. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol. 2006;176:1848–1859. doi: 10.4049/jimmunol.176.3.1848. [DOI] [PubMed] [Google Scholar]
  • 32.Burr GO, Burr MM. A new deficiency disease produced by the rigid exclusion of fat from the diet. J Biol Chem. 1929;82:345–367. doi: 10.1111/j.1753-4887.1973.tb06008.x. [DOI] [PubMed] [Google Scholar]
  • 33.Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA. 2004;101:8491–8496. doi: 10.1073/pnas.0402531101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Hong S, Tjonahen E, Morgan EL, Yu L, Serhan CN, Rowley AF. Rainbow trout (Oncorhynchus mykiss) brain cells biosynthesize novel docosahexaenoic acid-derived resolvins and protectins—mediator lipidomic analysis. Prostaglandins Other Lipid Mediat. 2005;78:107–116. doi: 10.1016/j.prostaglandins.2005.04.004. [DOI] [PubMed] [Google Scholar]

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