Advertisement

Lipoxins pp 51-59 | Cite as

Biosynthesis and Biological Activities of Lipoxin A5 and B5 from Eicosapentaenoic Acid

  • Bing K. Lam
  • Patrick Y.-K. Wong

Summary

[1-14C]- Eicosapentaenoic acid (EPA) was incubated with porcine leukocytes. Three polar metabolites were isolated after RP-HPLC separation in addition to pentaene leukotrienes and mono-hydroxy fatty acids. These compounds display U.V. absorbance with U.V. λmax at 302 nm with shoulders at 289 and 317 nm which were typical of a conjugated tetraenes. Using an alkaline RP-HPLC solvent system, it was found that these three compounds co-eluted with synthetic standards of lipoxin A5, lipoxin B5 and 5S, 6S, 15S-lipoxin A5 [6-S-LXA5] and were identified accordingly. Their structures were further confirmed by GC/MS analysis. When tested for biological activities, it was found that both lipoxin A5 and lipoxin B5 induce superoxide anion generation in canine neutrophils. Furthermore, LXA5 caused a dose-related contraction of isolated rat tail artery. The biological potency of 5-series lipoxins were similar to those of 4-series.

Keywords

Eicosapentaenoic Acid Superoxide Anion Generation Synthetic Standard Eicosatetraenoic Acid Lung Parenchymal Strip 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Serhan, C.N., Hamberg, M., and Samuelsson, B. Trihydroxytetraenes: A novel series of compounds formed from arachidonic acid in human leukocytes. Biochem. Biophys. Res. Commun., 118: 943–949 (1984)PubMedCrossRefGoogle Scholar
  2. 2.
    Serhan, C.N., Hamberg, M., and Samuelsson, B. Lipoxins: A novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc. Natl. Acad. Sci. U.S.A. 81: 5335–5339 (1984)PubMedCrossRefGoogle Scholar
  3. 3.
    Wong, P.Y-K., Hughes, R.A., and Lam, B. Lipoxene: A new group of trihydroxy pentaene of eicosapentaenoic acid derived from porcine leukocytes. Biochem. Biophys. Res. Commun. 126: 763–772 (1985)PubMedCrossRefGoogle Scholar
  4. 4.
    Serhan, C.N., Nicolaou, K.C., Webber, S.E., Veale, C.A., Dahlen, S.E., Puustinen, T.J., and Samuelsson, B. Lipoxin A: Stereochemistry and Biosynthesis. J. Biol. Chem. 261: 16340–16345 (1986)PubMedGoogle Scholar
  5. 5.
    Serhan, C.N., Hamberg, M., Samuelsson, B., Morris, J., and Wishka, D.G. On the stereochemistry and biosynthesis of lipoxin B. Proc. Natl. Acad. Sci. U.S.A. 83: 1983–1987 (1985)CrossRefGoogle Scholar
  6. 6.
    Murphy, R.C., Hammarstrom, B., and Samuelsson, B. Leukotriene C, a slow reacting substance from murine mastocytoma cells. Proc. Natl. Acad. Sci. U.S.A. 76: 4275–4279 (1979)PubMedCrossRefGoogle Scholar
  7. 7.
    Dahlen, S.E. Biological activities of lipoxins: FASEB Symposium on “Lipoxin: Biosynthesis and Pharmacology, Washington, D.C., March 30 (1987)Google Scholar
  8. 8.
    Lee, T.K. Biological activities of lipoxins of 5-series. FASEB Symposium on “Lipoxin: Biosynthesis and Pharmacology, Washington, D.C., March 30 (1987)Google Scholar
  9. 9.
    Hansson, A., Serhan, C.N., Haeggstrom, J., Ingelman-Sundberg, M., and Samuelsson, B. Activation of protein kinase C by lipoxin A and other eicosanoids. Intracellular action of oxygenation products of arachidonic acid. Biochem. Biophys. Res. Commun. 134: 1215–1222 (1986)Google Scholar
  10. 10.
    Ramstedt, U., Ng., J., Wigzell, H., Serhan, C.N., and Samuelsson, B. Action of novel eicosanoids lipoxin A and lipoxin B on human natural killer cell cytotoxicity: Effects on intracellular cAMP and target cell binding. J. Immunol. 135: 3434–3438 (1985)PubMedGoogle Scholar
  11. 11.
    Lam, B.K., Serhan, C.N., Samuelsson, B., and Wong, P.Y-K. A phospholipase A2 isoenzyme provokes lipoxin B formation from endogenous sources of arachidonic acid in porcine leukocytes. Biochem. Biophys. Res. Commun. 144: 123–131 (1987)PubMedCrossRefGoogle Scholar
  12. 12.
    Lam, B.K., Hirai, A., Yoshida, S., Tamura, Y., and Wong, P.Y-K. Transformation of 15-hydroperoxyeicosapentaenoic acid to lipoxin A5 and B5, mono-and dihydroxyeicosapentaenoic acids by porcine leukocytes. Biochim. Biophys. Acta. 917: 398–405 (1987)PubMedCrossRefGoogle Scholar
  13. 13.
    Ueda, N., Yamamoto, S., Fitzsimmons, B.J., and Rokach, J. Lipoxin synthesis by arachidonate 5-lipoxygenase purified from porcine leukocytes. Biochem. Biophys. Res. Commun. 144: 996–1002 (1987)PubMedCrossRefGoogle Scholar
  14. 14.
    Rouzer, C.A., Massumato, T., and Samuelsson, B. Single protein from human leukocytes possesses 5-lipoxygenase and leukotriene A4 synthetase activities. Proc. Natl. Acad. Sci. U.S.A. 83: 857–561 (1986)PubMedCrossRefGoogle Scholar
  15. 15.
    Yamamoto, S., Ueda, N., Yakoyama, C., Fitzsimmons, B.J., Rokach, J., Oates, J.A., and Brash, A.R. FASEB Symposium on “Lipoxin: Biosynthesis and Pharmacology, Washington, D.C., March 30 (1987)Google Scholar
  16. 16.
    Lam, B., Marcindiewicz, E., and Wong, P.Y-K. Transformation of 15-hydroperoxyeicosapetaenoic acid into mono-and dihydroperoxyeicosapentaenoic acids by human platelets. In: Drugs Affecting Leukotrienes and Other Eicosanoid Pathways. Edited by B. Samuelsson, F. Berti, G.C. Folco, and G.P. Velo. Plenum Publishing Corp., pp. 167–180 (1987)Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Bing K. Lam
    • 1
  • Patrick Y.-K. Wong
    • 1
  1. 1.Department of PharmacologyNew York Medical CollegeValhallaUSA

Personalised recommendations