Lipoxin Formation during Neutrophil-Platelet Interactions: a Role for Leukotriene A4 and Platelet 12-Lipoxygenase

  • C. N. Serhan
  • S. Fiore
  • K.-A. Sheppard
Part of the Developments in Oncology book series (DION, volume 67)


The lipoxins are a series of biologically active eicosanoids which contain a conjugated tetraene structure as a characteristic feature (1). The two main compounds which carry biological activities are positional isomers: one designated lipoxin A4 (5S,6R,15S-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid) and the other lipoxin B4 (5S,14R,15S, trihydroxy-6,10,12-trans-8-cis-eicosatetraenoic acid). Multiple pathways have been documented in vitro which can lead to the formation of lipoxins (1–4). It appears that the biosynthetic pathways utilized are species-, cell type- and substratespecific. One route, documented with results from both isotopic oxygen studies as well as the identification of alcohol trapping products, involves the transformation of 15-HETE to a 5(6)epoxytetraene by leukocytes (1). When this intermediate (15S-hydroxy-5,6-epoxy-7,9,13-trans-11-ciseicosatetraenoic acid) was synthesized and incubated with purified cytosolic epoxide hydrolase, it was quantitatively converted into LXA4 (5). During the formation of lipoxins from exogenous 15-HETE by human neutrophils (an event which may occur in cell-cell interactions), an inverse relationship is observed between leukotriene and lipoxin production (6). Thus, the generation of epoxide-containing intermediates by human PMN appears to play a pivotal role in the biosynthesis of both leukotrienes and lipoxins.


Positional Isomer Eicosatetraenoic Acid Isotopic Oxygen Study Active Eicosanoid Cytosolic Epoxide Hydrolase 
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  1. 1.
    Serhan, C.N. and Samuelsson, B. Adv. Exp. Med. Biol. 229:1–14, 1988.PubMedGoogle Scholar
  2. 2.
    Kuhn, H., Wiesner, R., Alder, L, Fitzsimmons, B.J., Rokach, J. and Brash, A.R. Eur. J. Biochem. 169:593–601, 1987.PubMedCrossRefGoogle Scholar
  3. 3.
    Ueda, N., Yokoyama, C, Yamamoto, S., Fitzsimmons, B.J., Rokach, J., Oates, J.A. and Brash, A.R. Biochem. Biophys. Res. Commun. 149:1063–1069, 1987.PubMedCrossRefGoogle Scholar
  4. 4.
    Walstra, P., Verhagen, J., Vermeer, M.A., Klerks, J.P.M., Veldink, G.A. and Vliegenthart, J.F.G. FEBS Lett. 228:167–171, 1988.PubMedCrossRefGoogle Scholar
  5. 5.
    Puustinen, T., Webber, S.E., Nicolaou, K.C., Haeggstrom, J., Serhan, C.N. and Samuelsson, B. FEBS Lett. 207:127, 1986.PubMedCrossRefGoogle Scholar
  6. 6.
    Serhan, C.N. Biochim. Biophys. Acta 1004:158–168, 1989.PubMedCrossRefGoogle Scholar
  7. 7.
    Dahinden, C.A., Clancy, R.M., Gross, M., Chiller, J.M. and Hugli, T.E. Proc. Natl. Acad. Sci. USA 82:6632–6636, 1985.PubMedCrossRefGoogle Scholar
  8. 8.
    Hamberg, M. Biochem. Biophys. Res. Commun. 117:593–600, 1983.PubMedCrossRefGoogle Scholar
  9. 9.
    Marcus, A.J., Broekman, M.J., Safier, L.B., Uliman, H.L., Islam, N., Serhan, C.N., Korchak, H. and Weissmann, G. Biochem. Biophys. Res. Commun. 109:130–137, 1982.PubMedCrossRefGoogle Scholar
  10. 10.
    Serhan,C.N. and Sheppard, K.A. 85:772–780, 1990.Google Scholar
  11. 11.
    Luscinskas, F.W., Nicolaou, K.C., Webber, S.E., Veale, C.A., Gimbrone, M.A., Jr. and Serhan, C.N. Biochem. Pharmacol., 39:355–365, 1990.PubMedCrossRefGoogle Scholar
  12. 12.
    Fiore, S. and Serhan, C.N. Biochem. Biophys. Res. Commun. 159:477–481, 1989.PubMedCrossRefGoogle Scholar
  13. 13.
    Sekiya, K., Okuda, H. and Arichi, S. Biochim. Biophys. Acta 713:68–72, 1982.Google Scholar
  14. 14.
    Corey, E.J. and Merrotra, M.M. Tetrahedron Lett. 27:5173–5176, 1986.CrossRefGoogle Scholar
  15. 15.
    Edenius, C, Haeggstrom, J. and Lindgren, J.A. Biochem. Biophys. Res. Commun. 157:801–807, 1988.PubMedCrossRefGoogle Scholar
  16. 16.
    Garrick, R., Shen, S.-Y., Ogunc, S. and Wong, P.Y.-K. Biochem. Biophys. Res. Commun. 162:626–633, 1989.PubMedCrossRefGoogle Scholar
  17. 17.
    Lee, T.H., Crea, A.E.G., Gant, V., Spur, B.W., Marron, B.E, Nicolaou, K.C., Reardon, E., Brezinski, M. and Serhan, C.N. (Submitted).Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • C. N. Serhan
    • 1
  • S. Fiore
    • 1
  • K.-A. Sheppard
    • 1
  1. 1.Hematology Division, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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