Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jul;80(13):4109–4113. doi: 10.1073/pnas.80.13.4109

Leukotriene C promotes prostacyclin synthesis by human endothelial cells.

E B Cramer, L Pologe, N A Pawlowski, Z A Cohn, W A Scott
PMCID: PMC394210  PMID: 6408642

Abstract

Cultured endothelial cells from human umbilical vein were labelled with [3H]arachidonic acid for 16 hr. The radiolabel was localized primarily in phospholipids (93%) and 73% was distributed equally between phosphatidylcholine and phosphatidylethanolamine. Leukotriene C (10-1,000 nM) promoted a dose-dependent release of radiolabel into the culture medium. This response was 3.3 times control values at 100 nM. The major arachidonic acid metabolite synthesized was prostacyclin, which was 33% of the total released radiolabel. Endothelial cells also released small amounts of prostaglandin F2 alpha (6.1%), unidentified lipoxygenase products (14.8%), and unreacted arachidonic acid (33%). The 30-min time course of release was independent of the leukotriene C concentration used. Leukotriene D at similar concentrations also promoted endothelial cells to release primarily prostacyclin and unreacted arachidonic acid. The release of prostacyclin, a potent vasodilator agent, may be an important mediator in slow reacting substance effects on the vasculature.

Full text

PDF
4109

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alam I., Ohuchi K., Levine L. Determination of cyclooxygenase products and prostaglandin metabolites using high-pressure liquid chromatography and radioimmunoassay. Anal Biochem. 1979 Mar;93(2):339–345. doi: 10.1016/s0003-2697(79)80160-8. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Baenziger N. L., Fogerty F. J., Mertz L. F., Chernuta L. F. Regulation of histamine-mediated prostacyclin synthesis in cultured human vascular endothelial cells. Cell. 1981 Jun;24(3):915–923. doi: 10.1016/0092-8674(81)90117-3. [DOI] [PubMed] [Google Scholar]
  4. Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CHAKRAVARTY N. A method for the assay of 'slow reacting substance'. Acta Physiol Scand. 1959 Aug 31;46:298–313. doi: 10.1111/j.1748-1716.1959.tb01760.x. [DOI] [PubMed] [Google Scholar]
  6. Dahlén S. E., Björk J., Hedqvist P., Arfors K. E., Hammarström S., Lindgren J. A., Samuelsson B. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3887–3891. doi: 10.1073/pnas.78.6.3887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dahlén S. E., Hedqvist P., Hammarström S., Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature. 1980 Dec 4;288(5790):484–486. doi: 10.1038/288484a0. [DOI] [PubMed] [Google Scholar]
  8. Hedqvist P., Dahlén S. E., Gustafsson L., Hammarström S., Samuelsson B. Biological profile of leukotrienes C4 and D4. Acta Physiol Scand. 1980 Nov;110(3):331–333. doi: 10.1111/j.1748-1716.1980.tb06676.x. [DOI] [PubMed] [Google Scholar]
  9. Hong S. L., Deykin D. Activation of phospholipases A2 and C in pig aortic endothelial cells synthesizing prostacyclin. J Biol Chem. 1982 Jun 25;257(12):7151–7154. [PubMed] [Google Scholar]
  10. Jaffe E. A., Hoyer L. W., Nachman R. L. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973 Nov;52(11):2757–2764. doi: 10.1172/JCI107471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jörg A., Henderson W. R., Murphy R. C., Klebanoff S. J. Leukotriene generation by eosinophils. J Exp Med. 1982 Feb 1;155(2):390–402. doi: 10.1084/jem.155.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keith A. D., Waggoner A. S., Griffith O. H. Spin-labeled mitochondrial lipids in Neurospora crassa. Proc Natl Acad Sci U S A. 1968 Nov;61(3):819–826. doi: 10.1073/pnas.61.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lewis R. A., Austen K. F. Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds. Nature. 1981 Sep 10;293(5828):103–108. doi: 10.1038/293103a0. [DOI] [PubMed] [Google Scholar]
  16. MacGlashan D. W., Jr, Schleimer R. P., Peters S. P., Schulman E. S., Adams G. K., 3rd, Newball H. H., Lichtenstein L. M. Generation of leukotrienes by purified human lung mast cells. J Clin Invest. 1982 Oct;70(4):747–751. doi: 10.1172/JCI110670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mahoney E. M., Hamill A. L., Scott W. A., Cohn Z. A. Response of endocytosis to altered fatty acyl composition of macrophage phospholipids. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4895–4899. doi: 10.1073/pnas.74.11.4895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pawlowski N. A., Scott W. A., Andreach M., Cohn Z. A. Uptake and metabolism of monohydroxy-eicosatetraenoic acids by macrophages. J Exp Med. 1982 Jun 1;155(6):1653–1664. doi: 10.1084/jem.155.6.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Piper P. J., Samhoun M. N., Tippins J. R., Morris H. R., Jones C. M., Taylor G. W. SRS-A and SRS: their structure, biosynthesis and actions. Int Arch Allergy Appl Immunol. 1981;66 (Suppl 1):107–112. doi: 10.1159/000232881. [DOI] [PubMed] [Google Scholar]
  21. Rastogi B. K., Nordøy A. Lipid composition of cultured human endothelial cells. Thromb Res. 1980 Jun 1;18(5):629–641. doi: 10.1016/0049-3848(80)90218-2. [DOI] [PubMed] [Google Scholar]
  22. Rouser G., Fkeischer S., Yamamoto A. Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids. 1970 May;5(5):494–496. doi: 10.1007/BF02531316. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Rouzer C. A., Scott W. A., Hamill A. L., Cohn Z. A. Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages. J Exp Med. 1982 Mar 1;155(3):720–733. doi: 10.1084/jem.155.3.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Samuelsson B. Leukotrienes: mediators of allergic reactions and inflammation. Int Arch Allergy Appl Immunol. 1981;66 (Suppl 1):98–106. doi: 10.1159/000232880. [DOI] [PubMed] [Google Scholar]
  26. Scott W. A., Zrike J. M., Hamill A. L., Kempe J., Cohn Z. A. Regulation of arachidonic acid metabolites in macrophages. J Exp Med. 1980 Aug 1;152(2):324–335. doi: 10.1084/jem.152.2.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smedegård G., Hedqvist P., Dahlén S. E., Revenäs B., Hammarström S., Samuelsson B. Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey. Nature. 1982 Jan 28;295(5847):327–329. doi: 10.1038/295327a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Swies J., Radomski M., Gryglewski R. J. Angiotensin-induced release of prostacyclin (PGI2) into circulation of anaesthetized cats. Pharmacol Res Commun. 1979 Sep;11(8):649–655. doi: 10.1016/s0031-6989(79)80055-7. [DOI] [PubMed] [Google Scholar]
  30. Thomas J. M., Chap H., Douste-Blazy L. Calcium ionophore A 23187 induces arachidonic acid release from phosphatidylcholine in cultured human endothelial cells. Biochem Biophys Res Commun. 1981 Dec 15;103(3):819–824. doi: 10.1016/0006-291x(81)90884-6. [DOI] [PubMed] [Google Scholar]
  31. Ueno A., Tanaka K., Katori M., Hayashi M., Arai Y. Species difference in increased vascular permeability by synthetic leukotriene C4 and D4. Prostaglandins. 1981 Apr;21(4):637–648. doi: 10.1016/0090-6980(81)90012-5. [DOI] [PubMed] [Google Scholar]
  32. Unger W. G., Stamford I. F., Bennett A. Extraction of prostaglandins from human blood. Nature. 1971 Oct 1;233(5318):336–337. doi: 10.1038/233336b0. [DOI] [PubMed] [Google Scholar]
  33. Weksler B. B., Ley C. W., Jaffe E. A. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187. J Clin Invest. 1978 Nov;62(5):923–930. doi: 10.1172/JCI109220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Williams T. J. Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation. Br J Pharmacol. 1979 Mar;65(3):517–524. doi: 10.1111/j.1476-5381.1979.tb07860.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES