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. 1982 Feb 1;155(2):390–402. doi: 10.1084/jem.155.2.390

Leukotriene generation by eosinophils

PMCID: PMC2186605  PMID: 6120203

Abstract

Horse eosinophils purified to greater than 98% generated slow reacting substance (SRS) when incubated with the calcium ionophore A23187. On a per cell basis, eosinophils generated four to five times the SRS produced by similarly treated horse neutrophils. Eosinophil SRS production was inhibited by 5,8,11,14-eicosatetraynoic acid and augmented by indomethacin and arachidonic acid, suggesting that it was a product(s) of the lipoxygenase pathway of arachidonic acid metabolism. Compounds with SRS activity were purified by high-pressure liquid chromatography (HPLC) and identified by ultraviolet spectra, spectral shift on treatment with lipoxygenase, incorporation of [14C]arachidonic acid, gas chromatography-mass spectrometry, and comparison of retention times on HPLC to authentic standards. The eosinophil products characterized were 5-(S), 12-(R)-dihydroxy-6-cis-8, 10-trans-14-cis-eicosatetraenoic acid (leukotriene B4) and its 5-(S), 12-(R)-6-trans and 5-(S), 12-(S)-6-trans isomers, 5-(S)-hydroxy-6-(R)-S- glutathionyl-7,9-trans-11, 14-cis-eicosatetraenoic acid (leukotriene C4) and its 11-trans isomer, and 5-(S)-hydroxy-6-(R)-S-cysteinylglycine- 7,9-trans-11,14-cis-eicosatetraenoic acid (leukotriene D4).

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Selected References

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  1. Augstein J., Farmer J. B., Lee T. B., Sheard P., Tattersall M. L. Selective inhibitor of slow reacting substance of anaphylaxis. Nat New Biol. 1973 Oct 17;245(146):215–217. doi: 10.1038/newbio245215a0. [DOI] [PubMed] [Google Scholar]
  2. Bach M. K., Brashler J. R., Hammarström S., Samuelsson B. Identification of a component of rat mononuclear cell SRS as leukotriene D. Biochem Biophys Res Commun. 1980 Apr 29;93(4):1121–1126. doi: 10.1016/0006-291x(80)90605-1. [DOI] [PubMed] [Google Scholar]
  3. Bach M. K., Brashler J. R., Hammarström S., Samuelsson B. Identification of leukotriene C-1 as a major component of slow-reacting substance from rat mononuclear cells. J Immunol. 1980 Jul;125(1):115–117. [PubMed] [Google Scholar]
  4. Borgeat P., Samuelsson B. Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem. 1979 Aug 25;254(16):7865–7869. [PubMed] [Google Scholar]
  5. Borgeat P., Samuelsson B. Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid. J Biol Chem. 1979 Apr 25;254(8):2643–2646. [PubMed] [Google Scholar]
  6. Clark D. A., Goto G., Marfat A., Corey E. J., Hammarström S., Samuelsson B. 11-Trans leukotriene C: a naturally occurring slow reacting substance. Biochem Biophys Res Commun. 1980 Jun 30;94(4):1133–1139. doi: 10.1016/0006-291x(80)90537-9. [DOI] [PubMed] [Google Scholar]
  7. Conroy M. C., Orange R. P., Lichtenstein L. M. Release of slow reacting substance of anaphylaxis (SRS-A) from human leukocytes by the calcium ionophore A23187. J Immunol. 1976 Jun;116(6):1677–1681. [PubMed] [Google Scholar]
  8. Drazen J. M., Austen K. F., Lewis R. A., Clark D. A., Goto G., Marfat A., Corey E. J. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4354–4358. doi: 10.1073/pnas.77.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Falkenhein S. F., MacDonald H., Huber M. M., Koch D., Parker C. W. Effect of the 5-hydroperoxide of eicosatetraenoic acid and inhibitors of the lipoxygenase pathway on the formation of slow reacting substance by rat basophilic leukemia cells; direct evidence that slow reacting substance is a product of the lipoxygenase pathway. J Immunol. 1980 Jul;125(1):163–168. [PubMed] [Google Scholar]
  10. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  11. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  12. Goetzl E. J., Pickett W. C. Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B. J Exp Med. 1981 Feb 1;153(2):482–487. doi: 10.1084/jem.153.2.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hammarström S., Murphy R. C., Samuelsson B., Clark D. A., Mioskowski C., Corey E. J. Structure of leukotriene C. Identification of the amino acid part. Biochem Biophys Res Commun. 1979 Dec 28;91(4):1266–1272. doi: 10.1016/0006-291x(79)91203-8. [DOI] [PubMed] [Google Scholar]
  14. Henderson W. R., Kaliner M. Mast cell granule peroxidase: location, secretion, and SRS-A inactivation. J Immunol. 1979 Apr;122(4):1322–1328. [PubMed] [Google Scholar]
  15. Horn B. R., Robin E. D., Theodore J., Van Kessel A. Total eosinophil counts in the management of bronchial asthma. N Engl J Med. 1975 May 29;292(22):1152–1155. doi: 10.1056/NEJM197505292922204. [DOI] [PubMed] [Google Scholar]
  16. Jakschik B. A., Kulczycki A., Jr, MacDonald H. H., Parker C. W. Release of slow reacting substance (SRS) from rat basophilic leukemia (RBL-1) cells. J Immunol. 1977 Aug;119(2):618–622. [PubMed] [Google Scholar]
  17. Jörg A., Portmann P., Fellay G., Dreyer J. L., Meyer J. A rapid and simple method for the isolation of pure eosinophilic leukocytes from horse blood. Experientia. 1978 Dec 15;34(12):1654–1656. doi: 10.1007/BF02034734. [DOI] [PubMed] [Google Scholar]
  18. Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morris H. R., Taylor G. W., Piper P. J., Samhoun M. N., Tippins J. R. Slow reacting substances (SRSs): the structure identification of SRSs from rat basophil leukaemia (RBL-1) cells. Prostaglandins. 1980 Feb;19(2):185–201. doi: 10.1016/0090-6980(80)90019-2. [DOI] [PubMed] [Google Scholar]
  20. Murphy R. C., Hammarström S., Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4275–4279. doi: 10.1073/pnas.76.9.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Murphy R. C., Hattox S. E., Helbig H. R. Application and evaluation of limited mass monitoring with a gas chromatograph mass spectrometer computer system. Biomed Mass Spectrom. 1978 Jul;5(7):444–452. doi: 10.1002/bms.1200050705. [DOI] [PubMed] [Google Scholar]
  22. Orning L., Hammarström S., Samuelsson B. Leukotriene D: a slow reacting substance from rat basophilic leukemia cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2014–2017. doi: 10.1073/pnas.77.4.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Palmer M. R., Mathews W. R., Hoffer B. J., Murphy R. C. Electrophysiological response of cerebellar Purkinje neurons to leukotriene D4 and B4. J Pharmacol Exp Ther. 1981 Oct;219(1):91–96. [PubMed] [Google Scholar]
  24. Parker C. W., Falkenhein S. F., Huber M. M. Sequential conversion of the glutathionyl side chain of slow reacting substance (SRS) to cysteinyl-glycine and cysteine in rat basophilic leukemia cells stimulated with A-23187. Prostaglandins. 1980 Nov;20(5):863–886. doi: 10.1016/0090-6980(80)90139-2. [DOI] [PubMed] [Google Scholar]
  25. Peck M. J., Piper P. J., Williams T. J. The effect of leukotrienes C4 and D4 on the microvasculature of guinea-pig skin. Prostaglandins. 1981 Feb;21(2):315–321. doi: 10.1016/0090-6980(81)90149-0. [DOI] [PubMed] [Google Scholar]
  26. Rouzer C. A., Scott W. A., Cohn Z. A., Blackburn P., Manning J. M. Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4928–4932. doi: 10.1073/pnas.77.8.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rouzer C. A., Scott W. A., Hamill A. L., Cohn Z. A. Dynamics of leukotriene C production by macrophages. J Exp Med. 1980 Nov 1;152(5):1236–1247. doi: 10.1084/jem.152.5.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Samuelsson B., Hammarström S., Murphy R. C., Borgeat P. Leukotrienes and slow reacting substance of anaphylaxis (SRS-A). Allergy. 1980 Jul;35(5):375–381. doi: 10.1111/j.1398-9995.1980.tb01782.x. [DOI] [PubMed] [Google Scholar]
  29. Sirois P., Borgeat P. From slow reacting substance of anaphylaxis (SRS-A) to leukotriene D4 (LTD4). Int J Immunopharmacol. 1980;2(4):281–293. doi: 10.1016/0192-0561(80)90028-4. [DOI] [PubMed] [Google Scholar]
  30. Sirois P., Borgeat P., Jeanson A., Roy S., Girard G. The action of leukotriene B4 (LTB4) on the lung. Prostaglandins Med. 1980 Dec;5(6):429–444. doi: 10.1016/0161-4630(80)90067-1. [DOI] [PubMed] [Google Scholar]
  31. Sok D. E., Pai J. K., Atrache V., Sih C. J. Characterization of slow reacting substances (SRSs) of rat basophilic leukemia (RBL-1) cells: effect of cysteine on SRS profile. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6481–6485. doi: 10.1073/pnas.77.11.6481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yecies L. D., Wedner H. J., Johnson S. M., Jakschik B. A., Parker C. W. Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. I. Conditions of generation and initial characterization. J Immunol. 1979 May;122(5):2083–2089. [PubMed] [Google Scholar]

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