Skip to main content
SpringerLink
Log in

The Leukotrienes: Mediators of Immediate Hypersensitivity Reactions and Inflammation

  • Chapter
Leukotrienes and Prostacyclin

Part of the book series: NATO Advanced Science Institutes Series ((NSSA,volume 54))

Summary

The leukotrienes (LT), originally discovered in leukocytes, are formed from polyunsaturated fatty acids as arachidonic acid. The unstable intermediate LTA4 (5(S)-oxido-trans-7,9-trans,11,14-cis-eicosatetraenoic acid), is converted enzymatically by hydrolysis Tinto LTB4 (5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraenoic acid), and by addition of glutathione into LTC4 (5(S)-hydroxy,6(R)-S-glutathionyl-7,9-trans,11,14-cis-eicosatetraenoic acid). LTC4 is metabolized to corresponding cystéinylglycine derivative (LTD4) and cysteine derivative (LTE4). Corresponding leukotrienes can be formed from 5,8,11-cis-eicosatrienoic acid and 5,8,11,14,17-cis-eicosapentaenoic acid. LTC4 LTD4 and LTE4 which are identical with slow reacting substance of anaphylaxis, are bronchoconstrictors and increase the permeability of microvasculature. LTB4 is a potent chemotactic agent and increases adhesion of leukocytes to endothelium in postcapillary venules. The leukotrienes might therefore function as mediators both in immediate hypersensitivity reactions and in inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Austen, K.F. (1978): Hemostasis of effector systems which can be recruited for immunological reactions. J. Immunol., 121: 793

    PubMed  CAS  Google Scholar 

  2. Bach, M.K., Brashler, J.R. and Gorman, R.R. (1977): On the structure of SRS-A: Evidence of biosynthesis from arachidonic acid. Prostaglandins, 14: 21.

    PubMed  CAS  Google Scholar 

  3. Bach, M.K., Brashler, J.R., Hammarström, S. and Samuelsson, B. (1980): Identification of leukotriene C-1 as a major component of slow reacting substance from rat mononuclear cells. J. Immunol., 125: 115.

    PubMed  CAS  Google Scholar 

  4. Bach, M.K., Brashler, J.R., Hammarström, S. and Samuelsson, B. (1980): Identification of a component of rat mononuclear cell SRS as leukotriene D. Biochem. Biophys. Res. Commun. 93: 1121.

    Article  PubMed  CAS  Google Scholar 

  5. Blackwell, G.J., Carnuccion, R., Di Rosa, M., Flower, R.J., Parente, L. and Persico, P. (1980): Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature (London), 287: 147.

    Article  CAS  Google Scholar 

  6. Borgeat, P., Hamberg, M. and Samuelsson, B. (1976): Transformation of arachidonic acid and homo- -linolenic acid by rabbit polymorphonuclear leukocytes. J. Biol. Chem. 251: 7816.

    PubMed  CAS  Google Scholar 

  7. Borgeat, P. and Samuelsson, B. (1979): Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. J. Biol. Chem. 254: 2643.

    PubMed  CAS  Google Scholar 

  8. Borgeat, P. and Samuelsson, B. (1979): Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J. Biol. Chem. 254: 7865.

    PubMed  CAS  Google Scholar 

  9. Borgeat, P. and Samuelsson, B. (1979): Arachidonic acid metabolism in polymorphonuclear leukocytes: Unstable intermediate in formation of dihydroxy acids. Proc. Natl. Acad. Sci. USA, 76: 3213.

    Article  PubMed  CAS  Google Scholar 

  10. Borgeat, P. and Samuelsson, B. (1979): Arachidonic acid metabolism in polymorphonuclear leukocytes: Effects of ionophore A23187. Proc. Natl. Acad. Sci. USA, 76: 2148.

    Article  PubMed  CAS  Google Scholar 

  11. Bray, M.A., Cunningham, F.M., Ford-Hutshinson, A.W. and Smith, M.J.H. (1981): Leukotriene B4: A mediator of vascular permeability. Br. J. Pharmacol. 72: 483.

    PubMed  CAS  Google Scholar 

  12. Brocklehurst, W.E. (1953): Occurrence of an unidentified substance during anaphylactic shock in cavy lung. J. Physiol. 120: 16P.

    Google Scholar 

  13. Brocklehurst, W.E. (1962): Slow Reacting Substance and Related Compounds. In:“Prog. Allergy” P. Kallos and B.H. Waksman, eds. vol. 6, pp. 539–558, Karger, Basel.

    Google Scholar 

  14. Conroy, M.D., Orange, R.P. and Lichtenstein, L.M. (1976): Release of slow reacting substance of anaphylaxis (SRS-A) from human leukocytes by the calcium ionophore A23187. J. Immunol. 116: 1677.

    PubMed  CAS  Google Scholar 

  15. Corey, E.J., Marfat, A., Goto, G. and Brion, F. (1981): Leukotriene B. Total synthesis and assignement of stereochemistry. J. Am. Chem. Soc. 102: 7984.

    Article  Google Scholar 

  16. Dahlén, S.E., Hedqvist, P., Hammarström, S. and Samuelsson, B. (1980): Leukotrienes are potent constrictors of human bronchi. Nature, 288: 484.

    Article  PubMed  Google Scholar 

  17. Dahlén, S.E., Björk, J., Hedqvist, P., Arfors, K.E., Hammarström, S., Lindgren, J.A. and Samuelsson, B. (1981): Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: In vivo effects with relevance to the acute inflammatory response. Proc. Natl. Acad. Sci. USA, 78: 3887.

    Article  PubMed  Google Scholar 

  18. Doig, M.V. and Ford-Hutshinson, A.W. (1980): The production and characterization of porducts of the lipoxygenase enzyme system released by rat peritoneal macrophages. Prostaglandins, 20: 1007.

    PubMed  CAS  Google Scholar 

  19. Drazen, J.M., Austen, F.K., Lewis, R.A., Clark, D.A., Goto, G., Marfat, A. and Corey, E.J. (1980): Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc. Natl. Acad. Sci. USA, 77: 4354.

    Article  PubMed  CAS  Google Scholar 

  20. Feldberg, W. and Kellaway, C.H. (1938): Liberation of histamine and formation of lysolecithin-like substances by cobra venom. J. Physiol. 94: 187.

    PubMed  CAS  Google Scholar 

  21. Folco, G., Hansson, G and Granström, E. (1981): Leukotriene C4 stimulates TXA2 formation in isolated sensitized guinea pig lungs. Biochem. Pharmacol. in press.

    Google Scholar 

  22. Ford-Hutchinson, A.W., Bray, M.A., Doig, M.V., Shipley, M.E. and Smith, M.J.H. (1980): Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature, 286: 264.

    Article  PubMed  CAS  Google Scholar 

  23. Ford-Hutchinson, A.W., Bray, M.A., Cunningham, F.M., Davidson, E.M. and Smith, M.J.H. (1981): Isomers of leukotriene B4 possess different biological potencies. Prostaglandins, 21: 143.

    PubMed  CAS  Google Scholar 

  24. Goetzl, E.J. and Pickett, W.C. (1980): The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs). J. Immunol., 125: 1789.

    PubMed  CAS  Google Scholar 

  25. Gryglewski, R., Panczeko, B., Korbut, R., Gordzinska, L. and Ocetkiewicz,A. (1975): Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins, 10: 343.

    PubMed  CAS  Google Scholar 

  26. Hammarström, S., Murphy, R.C., Samuelsson, B., Clark, D.A., Mioskowski, C. and Corey, E.J. (1979): Structure of leukotriene C. Identification of the amino acid part. Biochem. Biophys. Res. Commun. 91: 1266.

    Article  PubMed  Google Scholar 

  27. Hammarström, S., Samuelsson, B., Clark, D.A., Goto, G., Marfat, A., Mioskowski, C. and Corey, E.J. (1980): Stereo-chemistry of leukotriene C-1. Biochem. Biophys. Res. Commun. 92: 946.

    Article  PubMed  Google Scholar 

  28. Hammarström, S. and Samuelsson, B. (1980): Detection of leukotriene A4 as an intermediate in the biosynthesis of leukotriene C4 and D4. FEBS Lett., 122: 83.

    Article  Google Scholar 

  29. Hammarström, S. (1981): Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver and kidney. J. Biol. Chem. In press.

    Google Scholar 

  30. Hammarström, S., Bernström, K., Örning, L., Dahlén, S.E., Hedqvist, P., Smedegârd, G. and Revenäs, B. (1981): Rapid in vivo metabolism of leukotriene C3 in the monkey. Biochem. Biophys. Res. Commun. In press.

    Google Scholar 

  31. Hansson, G. and Râdmark, O. (1980): Leukotriene C4: Isolation from human polymorphonuclear leukocytes. FEBS Lett., 122: 87.

    Article  PubMed  CAS  Google Scholar 

  32. Hedqvist, P., Dahlén, S.E., Gustafsson, L., Hammarström, S. and Samuelsson, B. (1980): Biological profile of leukotrienes C4 and D4. Acta Physiol. Scand. 110: 331.

    Article  PubMed  CAS  Google Scholar 

  33. Hirata, F., Schiffmann, E., Venkatasubramanian, K., Salomon, D. and Axelrod, J. (1980): A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc. Natl. Acad. Sci. USA, 77: 2533.

    Article  PubMed  CAS  Google Scholar 

  34. Hong, S.C.L. and Levine, L. (1976): Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc. Natl. Acad. Sci. USA, 73: 1730.

    Article  PubMed  CAS  Google Scholar 

  35. Houglum, J., Pai, J.K., Atrache, V., Sok, D.E. and Sih, C.J. (1980): Identification of the slow reacting substance from cat paws. Proc. Natl. Acad. Sci. USA, 77: 5688.

    Article  PubMed  CAS  Google Scholar 

  36. Jakschik, B.A., Falkenhein, S. and Parker, C.W. (1977): Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells. Proc. Natl. Acad. Sci. USA, 74: 4577.

    Article  PubMed  CAS  Google Scholar 

  37. Jubiz, W., Râdmark, 0., Lindgren, J.A., Mlamsten, C. and Samuelsson, B. (1981): Novel leukotrienes: Products formed by initial oxygenation of arachidonic acid at C-15. Biochem. Biophys. Res. Commun. 99: 976.

    CAS  Google Scholar 

  38. Jubiz, W., Râdmark, O. and Samuelsson, B. (1981): Stimulation of leukotriene formation by formyl-methionyl-leucyl-phenylalamine (fMLP) in human leukocytes. FEBS Lett. In press.

    Google Scholar 

  39. Kellaway, C.H. and Trethewie, E.R. (1940): The liberation of a slow-reacting smooth muscle-stimulating substance in anaphylaxis. Q.J. Exp. Physiol. 30: 121.

    CAS  Google Scholar 

  40. Lewis, R.A., Drazen, J.M., Austen, K.F., Clark, D.A. and Corey, E.J. (1980): Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reaction substance of anaphylaxis (SRS-A). Importance of the 11-cis geometry for biological activity. Biochem. Biophys. Res. Commun. 96: 271.

    Article  CAS  Google Scholar 

  41. Lewis, R.A., Austen, K.F., Drazen, J.M., Clark, D.A., Marfat, A. and Corey, E.J. (1980): Slow reacting substances of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sources. Proc. Natl. Acad. Sci. USA, 77:3710.

    Article  PubMed  CAS  Google Scholar 

  42. Lindgren, J.A., Hansson, G. and Samuelsson, B. (1981): Formation of novel hydroxylated eicosatetraenoic acids in preparations of human polymorphonuclear leukocytes. FEBS Lett. 128: 329.

    Article  PubMed  CAS  Google Scholar 

  43. Lundberg, U., Râdmark, O., Malmsten, C. and Samuelsson, B. (1981): Transformation of 15-hydroperoxy-5,9,11,13-eicosatetraenoic acid into novel leukotrienes. FEBS Lett. 126: 127.

    Article  PubMed  CAS  Google Scholar 

  44. Malmsten, C.L., Palmblad, J., Udén, A.M., Râdmark, 0., Engstedt, L. and Samuelsson, B. (1980): Leukotriene B4: A highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes. Acta Physiol. Scand. 110: 449.

    Article  PubMed  CAS  Google Scholar 

  45. Morris, H.R., Taylor, G.W., Piper, P.J., Sirois, P. and Tippins, J.R. (1978): Slow-reacting substance of anaphylaxis. Purification and characterization. FEBS Lett., 87: 203.

    Article  PubMed  CAS  Google Scholar 

  46. Morris, H.R., Taylor, G.W., Piper, P.J., Samhoun, M.N. and Tippins, J.R. (1980): Slow reacting substances (SRSs): The structure identification of SRSs from rat basophilic leukemia (RBL-1) cells. Prostaglandins, 19: 185.

    PubMed  CAS  Google Scholar 

  47. Morris, H.R., Taylor, G.W., Piper, P.J. and Tippins, J.R. (1980): Structure of slow reacting substance of anaphylaxis from guinea pig lung. Nature, 285: 104.

    Article  PubMed  CAS  Google Scholar 

  48. Murphy, R., Hammarström, S., Samuelsson, B. (1979): Leukotriene C: A slow reacting substance from murine mastocytoma cells. Proc. Natl. Acad. Sci. USA, 76: 4275.

    Article  PubMed  CAS  Google Scholar 

  49. Orange, R.P. and Austen, K.F. (1969): Slow reacting substance of anaphylaxis. Adv. Immunol. 10: 104.

    Google Scholar 

  50. Orange, R.P., Murphy, R.C., Karnovsky, M.L. and Austen, K.F. (1973): The physiochemical characteristics and purification of SRS-A. J. Immunol. 110: 760.

    PubMed  CAS  Google Scholar 

  51. Orange, R.P., Murphy, R.C. and Austen, K.F. (1974): Inactivation av slow reacting substance of anaphylaxis (SRS-A) by arylsulfatases. J. Immunol. 113: 316.

    PubMed  CAS  Google Scholar 

  52. Urning, L., Hammarström, S. and Samuelsson, B. (1980): Leukotriene D: A slow reacting substance from rat basophilic leukemia cells. Proc. Natl. Acad. Sci. USA, 77: 2014.

    Article  Google Scholar 

  53. Palmblad, B., Malmsten, C.L., Udén, A.M., Râdmark, O., Engstedt, L. and Samuelsson, B. (1981): Leukotriene 84 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. Blood. In press.

    Google Scholar 

  54. Palmer, R.M.J., Stephney, R.J., Higgs, G.A. and Eakins, K.E. (1980): Chemokinetic activity of arachidonic acid lipoxygenase products on leukocytes of different species. Prostaglandins, 20: 411.

    PubMed  CAS  Google Scholar 

  55. Parker, C.W., Falkenhein, S.F. and Huber, M.M. (1980): Sequential conversion of the glutathionyl side chain of slow reacting substance (SRS) to cysteinyl-glycine and cysteine in rat basophilic leukemia cells stimulated with A23187. Prostaglandins, 20: 863.

    PubMed  CAS  Google Scholar 

  56. Peck, M.J., Piper, P.J. and Williams, T.J. (1981): The effect of leukotrienes C4 and D4 on the microvasculature of guinea pig skin. Prostaglandins, 21: 315.

    PubMed  CAS  Google Scholar 

  57. Râdmark, O., Malmsten, C., Samuelsson, B., Clark, D.A., Giichi, G., Marfat, A. and Corey, E.J. (1980): Leukotriene A: Stereo-chemistry and enzymatic conversion to leukoctriene B. Biochem. Biophys. Res. Commun. 92: 954.

    Article  PubMed  Google Scholar 

  58. Râdmark, O., Malmsten, C., Samuelsson, B., Goto, G., Marfat, A. and Corey, E.J. (1980): Leukotriene A: Isolation from human polymorphonuclear leukocytes. J. Biol. Chem. 255: 11828.

    PubMed  Google Scholar 

  59. Râdmark, O., Malmsten, C. and Samuelsson, B. (1980): Leukotriene A4: Enzymatic conversion to leukotriene C4. Biochem. Biophys. Res. Commun. 96: 1679.

    Article  PubMed  Google Scholar 

  60. Rouzer, C.A., Scott, W.H., Cohn, Z.A., Blackburn, P. and Manning, J.M. (1980): Mouse peritoneal macrophages release leukotriene C in response to a phagocytotic stimulus. Proc. Natl. Acad. Sci. USA, 77: 4928.

    Article  PubMed  CAS  Google Scholar 

  61. Samuelsson, B., Goldyne, M., Granström, E., Hamberg, M., Hammarström, S. and Malmsten, C. (1978): Prostaglandins and thromboxanes. Ann. Rev. Biochem. 47: 997.

    Article  PubMed  CAS  Google Scholar 

  62. Samuelsson, B., Borgeat, P., Hammarström, S. and Murphy, R.C. (1979): Introduction of nomenclature: Leukotrienes. Prostaglandins, 17: 785.

    PubMed  CAS  Google Scholar 

  63. Samuelsson, B., Hammarström, S., Murphy, R.C. and Borgeat, P. (1980): Leukotrienes and slow reacting substance of anaphylaxis (SRS-A). Allergy, 35: 375.

    Article  PubMed  CAS  Google Scholar 

  64. Samuelsson, B., Borgeat, P., Hammarström, S. and Murphy, R.C. (1980): Leukotrienes: A new group of biologically active compounds. In: B. Samuelsson, P. Ramwell and R. Paoletti, Eds. Advances in Prostaglandin and Thromboxane Research, vol. 6, Raven Press, New York, pp. 1–18.

    Google Scholar 

  65. Samuelsson, B. and Hammarström, S. (1980): Nomenclature for leukotrienes. Prostaglandins, 19: 645.

    PubMed  CAS  Google Scholar 

  66. Siegel, M.I., McConnell, R.T., Bonser, R.W. and Cautrecasas, P. (1981): The production of 5-HETE and leukotriene B in rat neutrophils from carrageenan pleural exudates. Prostaglandins, 21: 123.

    PubMed  CAS  Google Scholar 

  67. Smedegârd, G., Revenäs, B., Hedqvist, P., Dahlén, S.E., Hammarström, S. and Samuelsson, B. (1981): Cardiovascular and polmonary effects of leukotriene C4 in the monkey (Macaca Irus). Nature. Submitted.

    Google Scholar 

  68. Smith, M.J.H., Ford-Hutchinson, A.W. and Bray, M.A. (1980): Leukotriene B: A potent mediator of inflammation. J. Pharm. Pharmacol. 32, 517.

    Article  PubMed  CAS  Google Scholar 

  69. Strandberg, K. and Uvnäs, B. (1971): Purification and properties of the slow reacting substance formed in the cat paw perfused with compound 48/80. Acta Physiol. Scand. 82: 358.

    Article  CAS  Google Scholar 

  70. Vane, J.R. (1971): Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature (New Biol.), 231: 232.

    CAS  Google Scholar 

  71. Wedmore, C.V. and Williams, T.J. (1981): Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature, 289: 646.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiological, Chemistry Karolinska Institutet, S-104 01, Stockholm, Sweden

    Bengt Samuelsson

Authors
  1. Bengt Samuelsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Milan, Milan, Italy

    F. Berti  & G. Folco  & 

  2. University of Verona, Verona, Italy

    G. P. Velo

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Plenum Press, New York

About this chapter

Cite this chapter

Samuelsson, B. (1983). The Leukotrienes: Mediators of Immediate Hypersensitivity Reactions and Inflammation. In: Berti, F., Folco, G., Velo, G.P. (eds) Leukotrienes and Prostacyclin. NATO Advanced Science Institutes Series, vol 54. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4391-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-4391-2_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-4393-6

  • Online ISBN: 978-1-4684-4391-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation