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Quantitative Studies of the Lipid Mediators of Inflammation Using Liquid Chromatography-Electrospray Mass Spectrometry

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Molecular and Cellular Basis of Inflammation

Part of the book series: Current Inflammation Research ((CIRES))

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Abstract

The lipid mediators of inflammation include diverse biologically active molecules, mainly eicosanoids, but also phospholipids that modulate functional responses of inflammatory cells, i.e., adherence, locomotion, phagocytosis, production of reactive oxygen species, release of lysosomal enzymes, and synthesis of cytokines and other mediators. Lipid mediators also regulate important events of the inflammatory process, such as leukocyte trafficking, vascular permeability and smooth muscle contractility (1–3). Thus, lipid mediators play important roles in the regulation of the inflammatory process in health, in which they mediate immune response and promote tissue repair, as well as in inflammatory diseases, in which the dysregulation of their biosynthesis and/or activity results in tissue damage and other deleterious effects. Among many lipid mediators, PG E2 (PGE2), which is produced either by the constitutive cyclooxygenase (COX-1) or the inducible cyclooxygenase (COX-2), plays an important role in the regulation of phagocyte activity and acts as a potent vasodilator. Leukotriene B4 (LTB4) derived from the 5-lipoxygenase (5-LO) pathway is a potent chemoattractant for phagocytes and is likely an important component of body defense mechanisms against infection. LTB4 has also been recently involved in the development of inflammation in collagen-induced arthritis in mice (4), an animal model of rheumatoid arthritis. The cysteinyl-LT (LTC4, D4, and E4), also derived from the 5-LO pathway, are potent stimuli of vascular permeability and have been clearly implicated as mediators of the bronchospasm in asthma (5). Lipoxin A4 (LXA4), synthesized through the 5-LO and the 12- or 15-LO pathways, has been shown to act as a downregulator of phagocyte migration and is therefore believed to be part of the complex network of mediators that regulate leukocyte trafficking in inflammation (6).

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References

  1. Borgeat, P. and Naccache, P. H. (1990) Biosynthesis and biological activity of leukotriene B4. Clin. Biochem. 23, 459–468.

    Article  PubMed  CAS  Google Scholar 

  2. Serhan, C. N. and Drazen, J. M. (1997) Antiinflammatory potential of lipoxygenase-derived eicosanoids: a molecular switch at 5 and 15 positions? J. Clin. Invest. 99, 1147,1148.

    Article  PubMed  CAS  Google Scholar 

  3. Venable, M. E., Zimmerman, G. A., Mcintyre, T. M., and Prescott, S. M. (1993) Review—platelet-activating factor—a phospholipid autacoid with diverse actions. J. Lipid Res. 34, 691–702.

    PubMed  CAS  Google Scholar 

  4. Griffiths, R. J., Pettipher, E. R., Koch, K., Farrell, C. A., Breslow, R., Conklyn, M. J., Smith, M. A., Hackman, B. C., Wimberly, D. J., Milici, A. J., Scampoli, D. N., Cheng, J. B., Pillar, J. S., Pazoles, C. J., Doherty, N. S., Melvin, L. S., Reiter, L. A., Biggars, M. S., Falkner, F. C., Mitchell, D. Y., Liston, T. E., and Showell, H. J. (1995) Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. Proc. Natl Acad. Sci. USA 92, 517–521.

    Article  PubMed  CAS  Google Scholar 

  5. Hay, D. W. P., Torphy, T. J., and Undem, B. J. (1995) Cysteinyl leukotrienes in asthma: old mediators up to new tricks. Trends Pharmacol Sci. 16, 304–309.

    Article  PubMed  CAS  Google Scholar 

  6. Takano, T., Fiore, S., Maddox, J. F., Brady, H. R., Petasis, N. A., and Serhan, C. N. (1997) Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J. Exp. Med. 185, 1693–1704.

    Article  PubMed  CAS  Google Scholar 

  7. Mackert, G., Reinke, M., Schweer, H., and Seyberth, H. W. (1989) Simultaneous determination of the primary prostanoids prostaglandin E2, prostaglandin F2-alpha and 6-oxoprostaglandin-Fl—alpha by immunoaffinity chromatography in combination with negative ion chemical ionization gas chromatography TANDEM mass spectrometry. J. Chromatogr. Biomed. Appl. 494, 13–22.

    Article  CAS  Google Scholar 

  8. Callaghan, D. H., Yergey, J. A., Rousseau, P., and Masson, P. (1994) Respiratory tract eicosanoid measurement using microdialysis sampling and GC/MS detection. Pulmonary Pharmacol. 7, 35–41.

    Article  CAS  Google Scholar 

  9. Murphy, R. C. (1995) Lipid mediators, leukotrienes and mass spectrometry. J. Mass Spectrom. 30, 5–16.

    Article  CAS  Google Scholar 

  10. Borgeat, P. and Pilote, S. (1988) Rearrangement of 5S,12S-dihydroxy-6,8,10,14-(E,Z,E,Z)-eicosatetraenoic acid during gas Chromatographie analysis: formation of a cyclohexadiene derivative. Prostaglandins 35, 723–732.

    PubMed  CAS  Google Scholar 

  11. Balazy, M. and Murphy, R. C. (1986) Determination of sulfidopeptide leukotrienes in biological fluids by gas chromatography/mass spectrometry. Anal. Chem. 58, 1098–1101.

    Article  PubMed  CAS  Google Scholar 

  12. Shindo, K. and Hashimoto, Y. (1991) Quantitative analysis of platelet activating factor treated with pentafluorobenzoyl chloride using gas chromatography/negative ion chemical ionization mass spectrometry. Drugs Exp. Clin. Res. 17, 343–349.

    PubMed  CAS  Google Scholar 

  13. Borgeat, P., Picard, S., Vallerand, P., Bourgoin, S., Odeimat, A., Sirois, P., and Poubelle, P. E. (1990) Automated on-line extraction and profiling of lipoxygenase products of arachidonic acid by high performance liquid chromatography, in Methods in Enzymology: Arachidonate Related Lipid Mediators (Murphy, R. C. and Fitzpatrick, F., eds.), Academic, New York, pp. 98–116.

    Chapter  Google Scholar 

  14. Surette, M. E., Odeimat, A., Palmantier, R., Marleau, S., Poubelle, P. E., and Borgeat, P. (1994) Reverse-phase high-performance liquid chromatography analysis of arachidonic acid metabolites in plasma after stimulation of whole blood ex vivo. Anal. Biochem. 216, 392–400.

    Article  PubMed  CAS  Google Scholar 

  15. Powell, W. S. (1987) Precolumn extraction and reversed-phase high-pressure liquid chromatography of prostaglandins and leukotrienes. Anal Biochem. 164, 117–131.

    Article  PubMed  CAS  Google Scholar 

  16. Ramis, I., Hotter, G., Rosellocatafau, J., Bulbena, O., Picado, C., and Gelpi, E. (1993) Application of totally automated on-line sample clean up system for extraction and high-performance liquid chromatography separation of peptide leukotrienes. J. Pharmaceut. Biomed. Anal. 11, 1135–1139.

    Article  CAS  Google Scholar 

  17. Fritsch, H., Molnar, I., and Wurl, M. (1994) Separation of arachidonic acid metabolites by online extraction and reversed-phase high-performance liquid chromatography optimized by computer simulation. J. Chromatogr. A 684, 65–75.

    Article  CAS  Google Scholar 

  18. McGuffin, V. L. and Zare, R. N. (1985) Femtomole analysis of prostaglandin Pharmaceuticals. Proc. Natl Acad. Sci. USA 82, 8315–8319.

    Article  PubMed  CAS  Google Scholar 

  19. Salari, H., Yeung, M., Douglas, S., and Morozowich, W. (1987) Detection of prostaglandins by high-performance liquid chromatography after conversion to p-(9-anthroyloxy)phenacyl esters. Anal. Biochem. 164, 1–10.

    Article  Google Scholar 

  20. Hesse, W. H., Schweer, H., Seyberth, H. W., and Peskar, B. A. (1990) Separation and determination of prostaglandin El metabolites by high-performance liquid chromatography. J. Chromatogr. Biomed. Appl. 533, 159–165.

    Article  CAS  Google Scholar 

  21. Herderich, M., Richling, E., Roscher, R., Schneider, C., Schwab, W., Humpf, H. U., and Schreier, P. (1997) Application of atmospheric pressure ionization HPLC-MS-MS for the analysis of natural products. Chromatographia 45, 127–132.

    Article  CAS  Google Scholar 

  22. Kebarle, P. and Tang, L. (1993) From ions in solution to ions in the gas phase—the mechanism of electrospray mass spectrometry. Anal Chem. 65, A972–A986.

    Google Scholar 

  23. Margalit, A., Duffin, K. L., and Isakson, P. C. (1996) Rapid quantitation of a large scope of eicosanoids in two models of inflammation: development of an electrospray and tandem mass spectrometry method and application to biological studies. Anal. Biochem. 235, 73–81.

    Article  PubMed  CAS  Google Scholar 

  24. Wheelan, P. and Murphy, R. C. (1997) Quantitation of 5-lipoxygenase products by electrospray mass spectrometry: effect of ethanol on zymosan-stimulated production of 5-lipoxygenase products by human neutrophils. Anal. Biochem. 244, 110–115.

    Article  PubMed  CAS  Google Scholar 

  25. Kerwin, J. L., Wiens, A. M., and Ericsson, L. H. (1996) Identification of fatty acids by electrospray mass spectrometry and tandem mass spectrometry. J. Mass Spectrom. 31, 184–192.

    Article  PubMed  CAS  Google Scholar 

  26. Oda, Y., Mano, N., and Asakawa, N. (1995) Simultaneous determination of thromboxane B2, prostaglandin E2 and leukotriene B4 in whole blood by liquid chromatography mass spectrometry. J. Mass Spectrom. 30, 1671–1678.

    Article  CAS  Google Scholar 

  27. Wu, Y. H., Li, L. Y. T., Henion, J. D., and Krol, G. J. (1996) Determination of LTE4 in human urine by liquid chromatography coupled with ionspray tandem mass spectrometry. J. Mass Spectrom. 31, 987–993.

    Article  PubMed  CAS  Google Scholar 

  28. Kerwin, J. L. and Torvik, J. J. (1996) Identification of monohydroxy fatty acids by electrospray mass spectrometry and tandem mass spectrometry. Anal. Biochem. 237, 56–64.

    Article  PubMed  CAS  Google Scholar 

  29. Griffiths, W. J., Yang, Y., Sjövall, J., and Lindgren, J. A. (1996) 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. 10, 183–196.

    Article  PubMed  CAS  Google Scholar 

  30. Schneider, C., Schreier, P., and Herderich, M. (1997) Analysis of lipoxygenase-derived fatty acid hydroperoxides by electrospray ionization tandem mass spectrometry. Lipids 32, 331–336.

    Article  PubMed  CAS  Google Scholar 

  31. Silvestro, L., Dacol, R., Scappaticci, E., Libertucci, D., Biancone, L., and Camussi, G. (1993) Development of a high-performance liquid Chromatographic mass spectrometric technique, with an ionspray interface, for the determination of platelet-activating factor (PAF) and lyso-PAF in biological samples. J. Chromatogr. 647, 261–269.

    Article  PubMed  CAS  Google Scholar 

  32. Borgeat, P., Picard, S., Braquet, P., Allen, M., and Shushan, B. (1994) LC-MS-MS with ion spray: A promising approach for analysis of underivatized platelet activating factor (PAF). J. Lipid Media. Cell Signal. 10, 11,12.

    CAS  Google Scholar 

  33. Savu, S. R., Silvestro, L., Sorgel, F., Montrucchio, G., Lupia, E., and Camussi, G. (1996) Determination of l-o-acyl-2—acetyl-sn-glyceryl-3-phosphorylcholine, platelet-activating factor and related phospholipids in biological samples by high-performance liquid chromatography tandem mass spectrometry. J. Chromatogr. B 682, 35–45.

    Article  CAS  Google Scholar 

  34. Weintraub, S. T. and Pinckard, N. R. (1991) Electrospray ionization for analysis of platelet-activating factor. Rapid Commun. Mass Spectrom. 5, 309–311.

    Article  PubMed  CAS  Google Scholar 

  35. Olsson, N. U. and Salem, N. (1997) Molecular species analysis of phospholipids. J. Chromatogr B 692, 245–256.

    Article  CAS  Google Scholar 

  36. Han, X. L. and Gross, R. W. (1996) Structural determination of lysophospholipid regioisomers by electrospray ionization tandem mass spectrometry. J. Am. Chem. Soc. 118, 451–457.

    Article  CAS  Google Scholar 

  37. Surette, M. E., Palmantier, R., Gosselin, J., and Borgeat, P. (1993) Lipopolysaccharides prime whole human blood and isolated neutrophils for the increased synthesis of 5-lipoxygenase products by enhancing arachidonic acid availability—involvement of the CD14 antigen. J. Exp. Med. 178, 1347–1355.

    Article  PubMed  CAS  Google Scholar 

  38. Palmantier, R., Rocheleau, H., Laviolette, M., Mancini, J., and Borgeat, P. (1998) Characteristics of leukotriene synthesis by human granulocytes in presence of plasma. Biochim. Biophys. Acta 1389, 187–196.

    Article  PubMed  CAS  Google Scholar 

  39. Dieter, P. (1994) Arachidonic acid and eicosanoid release. J. Immunol. Methods 174, 223–229.

    Article  PubMed  CAS  Google Scholar 

  40. Dahinden, C. A., Zingg, J., Maly, F. E., and DeWeek, A. L. (1988) Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5a and FMLP as second signals. J. Exp. Med. 167, 1281–1295.

    Article  PubMed  CAS  Google Scholar 

  41. DiPersio, J. F., Naccache, P. H., Borgeat, P., Gasson, J. C., Nguyen, M.-H., and McColl, S. R. (1988) Characterization of the priming effects of human granulocyte-macrophage colony-stimulating factor on human neutrophil leukotriene synthesis. Prostaglandins 36, 673–691.

    PubMed  CAS  Google Scholar 

  42. Palmantier, R., Surette, M. E., Sanchez, A., Braquet, P., and Borgeat, P. (1994) Priming for the synthesis of 5-lipoxygenase products in human blood ex vivo by human granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. Lab. Invest. 70, 696–704.

    PubMed  CAS  Google Scholar 

  43. McColl, S. R., Krump, E., Naccache, P. H., Poubelle, P. E., Braquet, P., Braquet, M., and Borgeat, P. (1991) Granulocyte-macrophage colony-stimulating factor increases the synthesis of leukotriene B4 by human neutrophils in response to platelet-activating factor—enhancement of both arachidonic acid availability and 5-lipoxygenase activation. J. Immunol. 146, 1204–1211.

    PubMed  CAS  Google Scholar 

  44. Rola-Pleszczynski, M. (1985) Immunoregulation by leukotrienes and other lipoxygenase metabolites. Immunol. Today 6, 302–307.

    Article  CAS  Google Scholar 

  45. Yamaoka, K. A., Claesson, H. E., and Rosen, A. (1989) Leukotriene B4 enhances activation, proliferation, and differentiation of human lymphocytes B. J. Immunol. 143, 1996–2000.

    PubMed  CAS  Google Scholar 

  46. Claesson, H. E., Odlander, B., and Jakobsson, P. J. (1992) Leukotriene B4 in the immune system. Int. J. Immunopharmacol. 14, 441–449.

    Article  PubMed  CAS  Google Scholar 

  47. Rola-Pleszczynski, M. and Stankova, J. (1992) Leukotriene B4 enhances interleukin-6 (IL-6) production and IL-6 messenger RNA accumulation in human monocytes in vitro—transcriptional and posttranscriptional mechanisms. Blood 80, 1004–1011.

    PubMed  CAS  Google Scholar 

  48. Marleau, S., Dallaire, N., Poubelle, P. E., and Borgeat, P. (1994) Metabolic disposition of leukotriene B4 (LTB4) and oxidation-resistant analogues of LTB4 in conscious rabbits. Br. J. Pharmacol. 112, 654–658.

    Article  PubMed  CAS  Google Scholar 

  49. Smith, W. L., Garavito, R. M., and Dewitt, D. L. (1996) Prostaglandin endoperoxide h synthases (cyclooxygenases)-l and-2. J. Biol. Chem. 271, 33,157–33,160.

    Article  PubMed  CAS  Google Scholar 

  50. Niiro, H., Otsuka, T., Izuhara, K., Yamaoka, K., Ohshima, K., Tanabe, T., Hara, S., Nemoto, Y., Tanaka, Y., Nakashima, H., and Niho, Y (1997) Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils. Blood 89, 1621–1628.

    PubMed  CAS  Google Scholar 

  51. Pailiot, M., Gilbert, C., Bongeat, P., Poubelle, P. E., Bourgoin, S., Ghassi, J., Maclouf, J., McColl, S. R., and Naccache, P. H. (1998) Expression and activity of mastaglandin endoperoxide synthase-2 in agonist-actuated human neutrophils. FASEB J., in press.

    Google Scholar 

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Authors
  1. Pierre Borgeat
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  2. Serge Picard
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  3. Nancy Dallaire
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  4. Marc Pouliot
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  5. Marc E. Surette
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Editors and Affiliations

  1. Department of Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Charles N. Serhan

  2. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA

    Peter A. Ward

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Borgeat, P., Picard, S., Dallaire, N., Pouliot, M., Surette, M.E. (1999). Quantitative Studies of the Lipid Mediators of Inflammation Using Liquid Chromatography-Electrospray Mass Spectrometry. In: Serhan, C.N., Ward, P.A. (eds) Molecular and Cellular Basis of Inflammation. Current Inflammation Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-253-1_13

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  • DOI: https://doi.org/10.1007/978-1-59259-253-1_13

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-089-2

  • Online ISBN: 978-1-59259-253-1

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