Advertisement

Lipoxins pp 137-145 | Cite as

Effects of Lipoxins A and B on Functional Responses of Human Granulocytes

  • Jan Palmblad
  • Hans Gyllenhammar
  • Bo Ringertz

Abstract

The effects of synthetic lipoxin A and B (LXA and LXB) as well as several of their isomers were assessed as inducers of functional responses of human granulocytes. LXA stimulated migration at 1 nM and exhibited a variable effect as inducer of chemiluminescence at concentrations ≥ 1 μM. Both migration and chemiluminescence evoked by LXA proved to be highly stereospecific, since e.g. 6S-LXA was less active than LXA. Neither synthetic LXA nor several of its stereoisomers provoked degranulation, aggregation, membrane potential changes or intracellular calcium fluxes. In addition, LXB and its isomers did not stimulate aggregation, degranulation or chemiluminescence. Pretreatment of granulocytes with LXA did not modify subsequent challenges with leukotriene B4. Together, these results indicate that granulocyte responses to LXA are highly stereospecific and are mediated by other mechanisms than those evoked by leukotriene B4.

Keywords

Membrane Potential Change Spontaneous Migration Elastase Release Intracellular Calcium Flux Lung 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.
    Samuelsson B: Leukotrienes. Science 220: 568, 1983.CrossRefGoogle Scholar
  2. 2.
    Palmblad J, Malmsten CL, Udén A-M, RAdmark 0, Engstedt L, Samuelsson B: Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. Blood 44: 37, 1981.Google Scholar
  3. 3.
    Goetzl EJ, Pickett WC: The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs). J Immunol 125: 1789, 1980.PubMedGoogle Scholar
  4. 4.
    Dahlén SE, Björk J, Hedqvist P, Arfors KE, Hammarström S, Lindgren JA, Samuelsson B: Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules. Proc Natl Acad Sci USA 78: 3887, 1981.PubMedCrossRefGoogle Scholar
  5. 5.
    Ringertz B, Palmblad J, RAdmark 0, Malmsten CL: Leukotriene induced neutrophil aggregation in vitro. FEBS Lett 147: 180, 1982.PubMedCrossRefGoogle Scholar
  6. 6.
    Hafström I, Palmblad J, Malmsten CL, RAdmark 0, Samuelsson B: Leukotriene B4 - a stereospecific stimulator for release of lysosomal enzymes from neutrophils. FEBS Lett 130: 146, 1981.PubMedCrossRefGoogle Scholar
  7. 7.
    Feinmark S, Lindgren JA, Claesson HE, Malmsten CL, Samuelsson B: Stimulation of human leukocyte degranulation by leukotriene B4 and its u)-oxidized metabolites. FEBS Lett 136: 141, 1981.PubMedCrossRefGoogle Scholar
  8. 8.
    Palmblad J, Gyllenhammar H, Lindgren JA, Malmsten CL: Effects of leukotrienes and f-Met-Leu-Phe on oxidative metabolism of neutrophils and eosinophils. J Immunol 132: 3041, 1984.PubMedGoogle Scholar
  9. 9.
    Serhan CN, Radin A, Smolen JE, Korchak HM, Samuelsson B, Weissman G: Leukotriene B4 is a complete secretagogue in human neutrophils. A kinetic analysis. Biochem Biophys Res Commun 107: 1006, 1982.PubMedCrossRefGoogle Scholar
  10. 10.
    Serhan CN, Hamberg M, Samuelsson B. Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Nati Acad Sci USA 81: 5335–5339, 1984.CrossRefGoogle Scholar
  11. 11.
    Dahlén SE, Raud J, Serhan CN, Björk J, Samuelsson B: Biological activities of lipoxin A includes lung strip contraction and dilation of arterioles in vivo. Acta Physiol Scand 1987, in press.Google Scholar
  12. 12.
    Ramstedt U, Ng J, Wigzell H, Serhan CN, Samuelsson B: Action of novel eicosanoids lipoxin A and B on human natural killer cell cytotoxicity: effects on intracellular cAlTP and target cell binding. J Immunol 135: 3434, 1985.PubMedGoogle Scholar
  13. 13.
    Serhan CN, Nicolaou KC, Webber SE, Veale CA, Dahlén SE, Puustinen TJ, Samuelsson B: Lipoxin A: sterochemistry and biosynthesis. J Biol Chem 261: 16340, 1986.PubMedGoogle Scholar
  14. 14.
    Serhan CN, Hamberg M, Samuelsson B, Morris J, Wishka DG: On the stereo-chemistry and biosynthesis of lipoxin B. Proc Natl Acad Sci USA 83: 1983, 1986.PubMedCrossRefGoogle Scholar
  15. 15.
    Ramstedt U, Serhan CN, Nicolaou KC, Webber SE, Wigzell H, Samuelsson B: Lipoxin A induced inhibition of human natural killer cell cytotoxicity: Studies on stereospecifícity of inhibition and mode of action. J Immunol 138: 266, 1987.PubMedGoogle Scholar
  16. 16.
    Nicolaou KC, Veale CA, Webber SE, Katerinopoulos HK: Stereocontrolled total synthesis of lipoxin A. J Amer Chem Soc 107: 7515, 1985.CrossRefGoogle Scholar
  17. 17.
    Nicolaou KC, Webber SE: Stereocontrolled total synthesis of lipoxins B. Int J Methods Synth Org Chem 6: 453, 1986.Google Scholar
  18. 18.
    Gyllenhammar H, Ringertz B, Becker W, Svensson J, Palmblad J: Essential fatty acid deficiency in rats. Immunol Letters 13: 185, 1986.CrossRefGoogle Scholar
  19. 19.
    Smith CW, Hollers JC, Patrich RA, Hassett C: Motility and adhesiveness in human neutrophils. J Clin Invest 63: 221, 1979.PubMedCrossRefGoogle Scholar
  20. 20.
    Metcalf JA, Gallin JI, Nauseef WM, Root RK: Laboratory manuel of neutrophil function. Raven Press, New York, 1986.Google Scholar
  21. 21.
    Hansson A, Serhan CN, Haeggström J, Ingelman-Sundberg M, Samuelsson B: Activation of protein kinase C by lipoxin A and other eicosanoids. Biochem Biophys Res Commun 134: 1215, 1986.PubMedCrossRefGoogle Scholar
  22. 22.
    Nishihira J, McPhail LC, O’Flaherty JT: Stimulus-dependent mobilization of protein kinase C. Biochem Biophys Res Couuuun 134: 587, 1986.CrossRefGoogle Scholar
  23. 23.
    Seligmann BE, Fletcher MB, Gallin JI: Adaptation of human neutrophil responsiveness to the chemoattractant N-formylmethionylleucylphenylalanine. J Biol Chem 257: 6280, 1982.PubMedGoogle Scholar
  24. 24.
    Goldman DW, Goetzl EJ: Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. J Exp Med 159: 1027, 1984.PubMedCrossRefGoogle Scholar
  25. 25.
    Serhan CN, Bamberg M, Samuelsson B: Novel mechanisms in the arachidonic acid cascade: formation of lipoxins. In Adv Inflammation Res (ed F Russo-Marie et al). Raven Press, New York 10:117, 1985.Google Scholar
  26. 26.
    Gay JC, Beckman JK, Brash AR, Oates JA, Lukens JN: Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4. Blood 64: 780, 1984.PubMedGoogle Scholar
  27. 27.
    Palmblad J, Gyllenhammar H, Ringertz B, Serhan CB, Samuelsson B: The effects of lipoxin A and lipoxin B on functional responses of human granulocytes. Biochem Biophys Res Commun, in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Jan Palmblad
    • 1
  • Hans Gyllenhammar
    • 1
  • Bo Ringertz
    • 1
  1. 1.Dept. of Medicine 3Karolinska InstitutetStockholmSweden

Personalised recommendations